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Solitary fibrous tumor of the meninges

Case report and review of the literature

Richard A. Prayson, James T. McMahon and Gene H. Barnett

✓ The authors present the case of a left frontal solitary fibrous tumor of the meninges. The gross appearance of the tumor was very similar to that of a fibroblastic meningioma. Histological examination showed a mixture of spindle-shaped and round cells arranged in a collagen matrix. Immunohistochemical staining of the tumor demonstrated diffuse positive staining for CD34 and vimentin. The tumor displayed no positive staining for markers of muscle, epithelial, glial, or neurocrest differentiation or for estrogen and progesterone receptors. The MIB-1 labeling index (the percentage of positive staining tumor cell nuclei), a marker of cellular proliferation, was 1.1%. Ultrastructural studies support attributing a mesenchymal, rather than meningothelial, nature to the tumor. A differential diagnosis is discussed and a review of the literature on these rare tumors is presented.

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Sarel J. Vorster, Richard A. Prayson and Joung H. Lee

✓ Solitary fibrous tumor (SFT) is a neoplasm first described as a tumor of mesenchymal origin involving soft tissues. The authors provide a review of the literature with detailed pathological analysis and radiological description of SFTs involving the central nervous system.

The authors report a rare case of a SFT of the thoracic spine in an adult man presenting with myelopathy. Magnetic resonance imaging revealed a well-circumscribed, intradural, extramedullary mass at the T2–3 level. Histological examination demonstrated a proliferation of predominantly spindle-shaped cells with a collagen-matrix background. Immunohistochemical staining was positive for vimentin and CD34 and negative for S-100 and epithelial membrane antigen with an MIB-1 labeling index of 2.6%. Review of the literature revealed 10 cases in which this tumor, frequently found in the pleura, was involved in the central nervous system.

Although rare and their clinical significance as yet unknown, SFTs may be considered in the differential diagnosis of intradural spinal cord lesions. The natural history is also unknown, but these tumors appear to be biologically benign.

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Burak Sade, Richard A. Prayson and Joung H. Lee

✓ Gliosarcomas are bimorphic intraaxial tumors. Involvement of the skull base is highly unexpected. The authors present the case of a temporal lobe gliosarcoma with significant infratemporal fossa extension. This 55-year-old man presented with a 1-month history of severe progressive headache. Neurological examination was unremarkable except for bilateral papilledema. Magnetic resonance imaging revealed a 6-cm right temporal mass with extension into the infratemporal fossa. The patient underwent a right frontotemporal craniotomy together with drilling of the sphenoid ridge and middle fossa floor. The tumor consisted of intraaxial, intracranial as well as extradural, and extracranial components with extension to the posterolateral wall of the sphenoid sinus. It had a relatively well-circumscribed dissection plane. Gross-total resection was achieved, and the middle fossa floor was reconstructed using a rotated temporalis muscle flap. The postoperative course was uneventful except for hypesthesia in the distribution of the maxillary division of the right trigeminal nerve. The histopathological diagnosis was consistent with gliosarcoma. Radiotherapy and chemotherapy consisting of temozolomide were administered subsequently, and the patient was recurrence free 12 months after his initial diagnosis.

In the presence of a mass lesion with both intraaxial and extracranial involvement, gliosarcoma should be considered among the differential diagnoses. Aggressive resection should be attempted, including the use of skull base surgical techniques to ensure an optimal outcome. The effect of skull base involvement to the overall treatment and outcome of patients with gliosarcomas would be difficult to determine given the rare occurrence of these lesions in such locations.

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Jorge A. González-Martínez, Gabriel Möddel, Zhong Ying, Richard A. Prayson, William E. Bingaman and Imad M. Najm

Object

Nitric oxide has been associated with epileptogenesis. Previous studies have shown increased expression of N-methyl-d-aspartate (NMDA) subunit NR2B receptors in epileptic dysplastic human neocortex. The expression of neuronal nitric oxide synthase (nNOS), and its relation to this subunit NR2B in epileptic dysplastic tissue has never been addressed.

Methods

Ten patients with medically intractable epilepsy caused by focal cortical dysplasia (CD), and 2 patients with mesial temporal sclerosis (control group) underwent pre- and/or intraoperative invasive monitoring evaluations. Cortical samples from epileptogenic and nonepileptogenic areas were collected from each patient intraoperatively. Samples were processed for cresyl violet staining, immunocytochemical tests with nNOS, NeuN, and NR2B, and immunofluorescence analyses to evaluate colocalized immunoreactivity between nNOS and NR2B.

Results

. All samples obtained in the patients with epilepsy revealed CD in various degrees. In the nonepileptic sample group, cresyl violet staining revealed normal cortical architecture in 9 samples, but a mild degree of CD in 3. The density and intensity of nNOS-stained neurons was remarkably increased in the epileptic tissue compared with nonepileptic samples (p < 0.05). Two types of nNOS-stained neurons were identified: Type I, expressing strong nNOS immunoreactivity in larger neurons; and Type II, expressing weak nNOS immunoreactivity in slightly smaller neurons. Different from Type I neurons, Type II nNOS-stained neurons revealed immunoreactivity colocalized with NR2B antibody.

Conclusions

The overexpression of nNOS in the epileptic samples and the immunoreactivity colocalization between nNOS and NR2B may suggest a possible role of nNOS and NO in the pathophysiological mechanisms related to in situ epileptogenicity.

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Gregory E. Plautz, Gene H. Barnett, David W. Miller, Bruce H. Cohen, Richard A. Prayson, John C. Krauss, Mark Luciano and Suyu Shu

Ten patients with progressive primary or recurrent malignant glioma received systemic adoptive immunotherapy to determine the feasibility, toxicity, and potential therapeutic benefits of this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of mediating the regression of experimental brain tumors in animal models. A rich source of tumor-immune T cells are lymph nodes (LNs) draining the tumor vaccine site. In this clinical study, patients were inoculated intradermally with irradiated autologous tumor cells and granulocyte-macrophage colony stimulating factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7 days after vaccination, were stimulated sequentially with staphylococcal enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used to expand the stimulated cells. The maximum cell proliferation was 350-fold over 10 days of culture. The activated cells were virtually all T cells consisting of various proportions of CD4 and CD8 cells. These cells were given to patients by intravenous infusion at doses ranging from 9 X 108 to 1.5 X 1011. There were no Grade 3 or 4 toxicities associated with the treatment. Following T cell transfer therapy, radiographic regression that lasted at least 4 months was demonstrated in three patients with recurrent tumors, and four patients remain alive more than 11 months after surgery. The remaining patients had progressive disease, and three patients required intervention with corticosteroid agents or additional surgery approximately 1 month following cell transfer. These findings demonstrate that adoptive immunotherapy can be administered in patients with glioma without causing significant toxicity. It appears that this experimental regimen can provide therapeutic benefits for some patients.

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Concurrent lymphocytic hypophysitis and pituitary adenoma

Case report and review of the literature

Shaye I. Moskowitz, Amir Hamrahian, Richard A. Prayson, Mercedes Pineyro, Robert R. Lorenz and Robert J. Weil

✓Lymphocytic hypophysitis (LyH) is an uncommon intrasellar lesion characterized by lymphocytic infiltration of the adenohypophysis. Evidence suggests that the cause is autoimmune, and the symptoms are usually related to either a mass effect or endocrine dysfunction. Lymphocytic hypophysitis has been described rarely in the setting of other simultaneous pathological processes that involve the pituitary and sella turcica, and is postulated to arise from an intrinsic inflammatory response.

The authors report the case of a 43-year-old woman who presented with a 2-month history of galactorrhea and pseudohyperprolactinemia secondary to a 10-mm lesion within an enlarged pituitary gland. She was nulliparous and had no contributory medical history. Serial neuroimaging performed over a 2-year period demonstrated lesion growth, and visual deficits had developed; together these warranted surgical intervention. A transsphenoidal resection was performed. Microscopic and immunohistopathological examinations revealed a nonsecreting pituitary adenoma with concurrent lymphocytic adenohypophysitis.

This is the first documented case of LyH in the setting of a null-cell pituitary adenoma. The authors review the related literature and outline potential mechanisms for the concurrent development of LyH and a pituitary adenoma.

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Jorge A. González-Martínez, Zhong Ying, Richard Prayson, William Bingaman and Imad Najm

Object

Changes in the expression of glutamate transporters (GLTs) may play a role in the expression of epileptogenicity. Previous studies have shown an increased number of neuronal GLTs in human dysplastic neurons. The expression of glial and neuronal GLTs and glutamine synthetase (GS) in balloon cells (BCs) and BC-containing cortical dysplasia has not been studied.

Methods

The authors analyzed neocortical samples that were resected in 5 patients who had cortical dysplasia–induced medically intractable focal epilepsy and who underwent extraoperative prolonged electrocorticographic (ECoG) recordings. The expressions of glial (GLT1/EAAT2) and neuronal (EAAT3, EAAC1) GLTs and GS proteins were immunohistochemically studied in all 5 resected samples. The authors also assessed in situ colocalization of GLTs and GS with neuronal and glial markers.

Results

Balloon cell–containing cortical dysplasia lesions did not exhibit ictal patterns on prolonged extraoperative ECoG recordings. There was a differential expression of glial and neuronal GLTs in BCs and dysplastic neurons: the majority of BCs highly expressed glial but not neuronal GLTs. Dysplastic neurons showed increased immunohistochemical staining with neuronal EAAT3 but not with EAAT2/GLT1. Moreover, only glial fibrillary acidic protein–positive BCs also expressed GS.

Conclusions

There is a differential GLT expression in dysplastic and balloon cells. The presence of glial GLTs and GS in balloon cell cortical dysplasia suggests a possible antiepileptic role for BCs and is consistent with the reported increased epileptogenicity in GLT1-deficient animals.

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William E. Thorell, Michael M. Chow, Richard A. Prayson, Mark A. Shure, Sung W. Jeon, David Huang, Emil Zeynalov, Henry H. Woo, Peter A. Rasmussen, Andrew M. Rollins and Thomas J. Masaryk

Object. Aneurysmal subarachnoid hemorrhage affects approximately 10/100,000 people per year. Endovascular coil embolization is used increasingly to treat cerebral aneurysms and its safety and durability is rapidly developing. The long-term durability of coil embolization of cerebral aneurysms remains in question; patients treated using this modality require multiple follow-up angiography studies and occasional repeated treatments.

Methods. Optical coherence tomography (OCT) is an emerging imaging modality that uses backscattered light to produce high-resolution tomography of optically accessible biological tissues such as the eye, luminal surface of blood vessels, and gastrointestinal tract. Vascular OCT probes in the form of imaging microwires are presently available—although not Food and Drug Administration—approved—and may be adapted for use in the cerebral circulation. In this study the authors describe the initial use of OCT to make visible the neck of aneurysms created in a canine model and treated with coil embolization. Optical coherence tomography images demonstrate changes that correlate with the histological findings of healing at the aneurysm neck and thus may be capable of demonstrating human cerebral aneurysm healing.

Conclusions. Optical coherence tomography may obviate the need for subsequent follow-up angiography studies as well as aid in the understanding of endovascular tissue healing. Data in this study demonstrate that further investigation of in vivo imaging with such probes is warranted.

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Gregory E. Plautz, Gene H. Barnett, David W. Miller, Bruce H. Cohen, Richard A. Prayson, John C. Krauss, Mark Luciano, Debra B. Kangisser and Suyu Shu

Object. To determine the feasibility, toxicity, and potential therapeutic benefits of systemic adoptive immunotherapy, 10 patients with progressive primary or recurrent malignant glioma received this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of mediating the regression of experimental brain tumors in animal models. In animal models, lymph nodes (LNs) that drain the tumor vaccine site are a rich source of tumor-immune T cells.

Methods. In this clinical study, patients were inoculated intradermally with irradiated autologous tumor cells and granulocyte macrophage-colony stimulating factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7 days after vaccination, were stimulated sequentially with staphylococcal enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used to expand the stimulated cells. The maximum cell proliferation was 350-fold over 10 days of culture. The activated cells were virtually all T cells consisting of various proportions of CD4 and CD8 cells. These cells were given to patients by intravenous infusion at doses ranging from 9 × 108 to 1.5 × 1011. There were no Grade 3 or 4 toxicities associated with the treatment. Following T-cell transfer therapy, radiographic regression that lasted at least 6 months was demonstrated in two patients with recurrent tumors. One patient demonstrated stable disease that has lasted for more than 17 months. The remaining patients had progressive disease; however, four of the eight patients with recurrent tumor remain alive more than 1 year after surgery for recurrence. Three patients required intervention with corticosteroid agents or additional surgery approximately 1 month following cell transfer.

Conclusions. These intriguing clinical observations warrant further trials to determine whether this approach can provide therapeutic benefits and improve survival.

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Samuel T. Chao, Taisei Kobayashi, Edward Benzel, Chandana A. Reddy, Glen H. J. Stevens, Richard A. Prayson, Iain Kalfas, Richard Schlenk, Ajit Krishnaney, Michael P. Steinmetz, William Bingaman, Joseph Hahn and John H. Suh

Object

The goal in this study was to determine the role of radiation therapy (RT) in the treatment of spinal myxopapillary ependymomas (MPEs).

Methods

Thirty-seven patients with histologically verified spinal MPEs were reviewed. Kaplan-Meier analyses and Cox proportional hazard regression were used to determine what patient and treatment factors influenced overall survival (OS) and recurrence.

Results

At the time of initial diagnosis, the median age was 33 years and the Karnofsky Performance Scale score was 80. In 86.5% of cases, the most common presenting symptom was pain. All patients received surgery as their initial treatment. Nine patients also received RT along with surgery, with a median total dose of 50.2 Gy. The mean survival time was 12.2 years; however, only 4 of 37 patients had died at the time of this study. None of the patient or treatment parameters significantly correlated with OS. Sixteen patients (43.2%) were found to have a recurrence, with a median time to recurrence of 7.7 years. None of the patient or treatment parameters correlated with recurrence-free survival for an initial recurrence. The median time to the second recurrence (recurrence following therapy for initial recurrence) was 1.6 years. Use of RT as salvage therapy after initial recurrence significantly correlated with longer times to a second recurrence. The median recurrence-free survival time before the second recurrence was 9.6 years for those who received RT versus 1.1 years for those who did not receive RT (p = 0.0093). None of the other parameters significantly correlated with a second recurrence.

Conclusions

Radiation therapy may have a role as salvage therapy in delaying recurrences of spinal MPEs.