✓ 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.
Case report and review of the literature
Richard A. Prayson, James T. McMahon, and Gene H. Barnett
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.
Case report and review of the literature
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.
Case report and review of the literature
Kene Ugokwe, Narendra Nathoo, Richard Prayson, and Gene H. Barnett
✓ Ancient change in a schwannoma is a histological variant typically found in longstanding tumors. Histologically, the tumor has biphasic features typical of a schwannoma with evidence of degenerative changes that may complicate diagnosis. The authors report on a 23-year-old man with no features of neurofibromatosis who presented with headaches, blurred vision, and ataxic gait. Magnetic resonance imaging demonstrated a rim-enhancing lesion in the cerebellopontine angle with displacement of brainstem structures and no supratentorial hydrocephalus. Using a lateral suboccipital approach together with image guidance and intraoperative neurophysiological monitoring, a gross-total macroscopic excision was performed. At surgery, the tumor was found to arise from the inferior division of the trigeminal nerve. The final histological diagnosis was schwannoma with ancient change. Note that ancient change in schwannomas is a histological variant thought to result from degenerative changes in longstanding tumors. To the authors' knowledge, this is the first independent report of this histological variant in an intracranial schwannoma.
Joung H. Lee, Burak Sade, Eugene Choi, Mladen Golubic, and Richard Prayson
This study was undertaken to test a hypothesis that meningiomas of the midline skull base and spine are predominantly of the meningothelial histological subtype.
The cases of 794 consecutive patients who underwent resection for meningioma at the Cleveland Clinic between January 1991 and March 2004 were reviewed retrospectively. The authors analyzed the relationship between the tumors’ histological subtypes and sites of origin in the 731 patients from this group who harbored tumors that were determined to be benign histologically (World Health Organization Grade I).
Meningothelial meningiomas (MMs) accounted for 63.5% (464/731) of the Grade I tumors. The incidence of MM according to the site of origin was as follows: 84.9% (186/219) in the midline skull base, 58.3% (35/60) in the lateral skull base, 48.5% (183/377) in a non–skull base location, and 80% (60/75) in spinal locations. The incidence of MM in the midline skull base and spinal locations were significantly higher than in non–skull base or lateral skull base locations.
Meningiomas of the midline neuraxis are predominantly meningotheliomas. Analysis of the increasingly available data on genetic and topographic characteristics of MMs suggests that they may represent a unique entity, contrary to the prevailing belief that all benign meningiomas are identical tumors.
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.
Jorge A. González-Martínez, Zhong Ying, Richard Prayson, William Bingaman, and Imad Najm
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.
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.
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.
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.
Thandar Aung, Vineet Punia, Masaya Katagiri, Richard Prayson, Irene Wang, and Jorge A. Gonzalez-Martinez
The objective of this study was to illustrate the feasibility and value of extra- and intraoperative stereoelectroencephalography (SEEG) in patients who underwent resection in rolandic and perirolandic regions.
The authors retrospectively reviewed all consecutive patients with at least 1 year of postoperative follow-up who underwent extra- and intraoperative SEEG monitoring between January 2015 and January 2017.
Four patients with pharmacoresistant rolandic and perirolandic focal epilepsy were identified, who underwent conventional extraoperative invasive SEEG evaluations followed by adjuvant intraoperative SEEG recordings. Conventional extraoperative SEEG evaluations demonstrated ictal and interictal epileptiform activities involving eloquent rolandic and perirolandic cortical areas in all patients. Following extraoperative monitoring, patients underwent preplanned staged resections guided by simultaneous and continuous adjuvant intraoperative SEEG monitoring. Resections, guided by electrode contacts of interest in 3D boundaries, were performed while continuous real-time electrographic data from SEEG recordings were obtained. Staged approaches of resections were performed until there was intraoperative resolution of synchronous rolandic/perirolandic cortex epileptic activities. All patients in the cohort achieved complete seizure freedom (Engel class IA) during the follow-up period ranging from 18 to 50 months. Resection resulted in minimal neurological deficit; 3 patients experienced transient, distal plantar flexion weakness (mild foot drop).
The seizure and functional outcome results of this highly preselected group of patients testifies to the feasibility and demonstrates the value of the combined benefits of both intra- and extraoperative SEEG recordings when resecting the rolandic and perirolandic areas. The novel hybrid method allows a more refined and precise identification of the epileptogenic zone. Consequently, tailored resections can be performed to minimize morbidity as well as to achieve adequate seizure control.
Jorge A. González-Martínez, Gabriel Möddel, Zhong Ying, Richard A. Prayson, William E. Bingaman, and Imad M. Najm
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.
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.
. 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.
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.
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.