Intracranial Epidural Metastases of Adrenal Pheochromocytoma: A Rare Entity.

BACKGROUND: Pheochromocytomas are uncommon neuroendocrine tumors of the adrenal medulla. Malignant behavior is seen in approximately 10% of these lesions, evidenced by distant metastasis to sites without chromaffin tissue. Here we report a rare case of intracranial epidural metastases of an adrenal pheochromocytoma in a 24-year-old man. CASE DESCRIPTION: The patient originally presented at age 10 years with adrenal pheochromocytoma and subsequently developed extensive metastatic bone and lung disease. He was monitored in the intervening years until recent imaging demonstrated an enlarging right parietal mass. On surgical resection of the parietal lesion, the tumor was highly vascularized and confined to the epidural space. CONCLUSIONS: To the best of our knowledge, this is the first reported case of metastatic epidural spread of pheochromocytoma without concomitant subdural or intraparenchymal extension.

Sellar Wegener Granulomatosis Masquerading as Cabergoline-Resistant Prolactinoma.

BACKGROUND: Pituitary manifestation of Wegener granulomatosis (WG) is extremely rare. When there is pituitary involvement, the granulomatous inflammatory lesions involving the pituitary gland may appear several months to years after the primary diagnosis. CASE DESCRIPTION: We present a case of a 32-year-old woman who presented with galactorrhea, amenorrhea, and elevated serum prolactin levels. Imaging demonstrated a sellar lesion with characteristics of a pituitary macroadenoma. Treatment with cabergoline was initiated, but the tumor continued to grow during a 6-month period. Subsequent surgical exploration revealed a chronic inflammatory lesion; the patient subsequently was diagnosed with WG based on laboratory evaluation and further systemic manifestations. She had a favorable clinical and radiologic response with immunosuppressive doses of glucocorticoids and rituximab. CONCLUSIONS: This case appears to be the first reported of a patient with unknown WG in whom the diagnosis was established after she presented with a sellar lesion mimicking a prolactin-secreting pituitary adenoma on initial presentation requiring surgical resection. The only endocrine abnormality discovered was moderate hyperprolactinemia. Sellar lesions with only moderate elevations in serum prolactin, particularly those that are refractory to medical management with a dopamine agonist, should prompt further investigation to confirm the diagnosis. WG should be part of the differential diagnosis of inflammatory lesions in the sella, the identification of which can facilitate early diagnosis and treatment of this systemic disease for optimal outcome.

Primary Intracranial Epidermoid Carcinoma with Diffuse Leptomeningeal Carcinomatosis: Report of Two Cases.

BACKGROUND: Malignant degeneration of epidermoid cyst (EC) with accompanying leptomeningeal carcinomatosis (LC) at presentation is extremely rare. We add two cases to the literature, including the first case of primary brainstem involvement with simultaneous diffuse LC, and discuss clinical and radiological cues to differentiate benign and malignant epidermoid tumors for early diagnosis. CASE DESCRIPTION: The first patient in this report was a 54-year-old woman with recurrent aseptic meningitis and hydrocephalus. Imaging revealed a prepontine and parapontine extra-axial EC with an intra-axial brainstem ring-enhancing cystic lesion, diffuse leptomeningeal enhancement, and intradural extramedullary nodular deposits throughout the spine. Surgical decompression of the cysts confirmed the diagnosis of invasive primary squamous cell carcinoma of the brainstem and benign epidermoid tumor of the cerebellopontine cistern. The second patient was a 37-year-old woman with extensive left-sided cranial neuropathies. Imaging revealed prepontine and parapontine enhancing and nonenhancing deposits along multiple cranial nerves and diffuse leptomeningeal nodular enhancement in the thoracolumbar spine. A biopsy confirmed the diagnosis of infiltrative, poorly differentiated carcinoma adjacent to a benign EC. Both patients underwent systemic screening to rule out metastatic disease. CONCLUSIONS: These cases illustrate that a high index of clinical suspicion is necessary for early diagnosis of disseminated disease in cases of recurrent episodes of aseptic meningitis. In cases of primary benign EC, aggressive resection should be attempted to reduce the risk of malignant degeneration. A separate biopsy specimen from the enhancing portion of the tumor is used to rule out an underlying coexisting malignancy. Multimodal management carries the best prognosis for primary intracranial squamous cell carcinoma with LC.

Giant Spontaneous Epidural Pneumatocele: Case Report and Review of the Literature.

BACKGROUND: Pneumocephalus is a commonly encountered finding in neurosurgery in which air displaces intracranial cerebrospinal fluid after cranial surgery or a cerebrospinal fluid leak into paranasal or mastoid sinuses. When an intracranial air collection becomes chronically established in a fixed loculation causing mass effect, pneumatocele is a more appropriate term. We present an unusual case of a spontaneous giant frontotemporal epidural pneumatocele that persisted for more than 1 year before the patient presented for neurological treatment. CASE DESCRIPTION: A 40-year-old man with a remote history of minor head trauma presented with symptoms of headaches, dizziness, and vertigo. Imaging revealed a right giant epidural pneumocephalus secondary to bony dehiscence of the intracranial wall of the mastoid bone. A subtemporal middle fossa approach was performed to repair the mastoid defect with hydroxyapatite, fat graft, and temporalis fascia. The patient was discharged on postoperative day 2 with improvement in his headaches. One month after discharge operative imaging demonstrated complete resolution of his epidural pneumatocele and improvement in his headaches. CONCLUSIONS: This unique case represents the first reported case in the neurosurgical literature of a giant spontaneous epidural pneumatocele occurring in an adult treated with a middle fossa approach with resolution on follow-up imaging.

Optic nerve hemangioblastoma: a case report.

Hemangioblastomas are World Health Organization (WHO) grade I tumors of uncertain histologic origin. These central nervous system tumors are most often found in the posterior fossa, brainstem, and spinal cord. There are fewer than 20 reported cases of optic nerve hemangioblastomas in the literature. We present a patient with visual decline found to have a mass arising from within the posterior orbital canal that grossly involved the optic nerve sheath. Neuropathologic evaluation showed hemangioblastoma. Although not a common tumor in this location, consideration of hemangioblastoma in the differential diagnosis is important as they can have a more aggressive course than other tumors of this region and have a detrimental effect on visual prognosis.

Chronic granulomatous herpes encephalitis in a child with clinically intractable epilepsy.

Most patients with herpes simplex virus Type I encephalitis experience an acute, monophasic illness. Chronic encephalitis is much less common, and few late relapses are associated with intractable seizure disorders. A 10-year-old boy was admitted to our institution for intractable epilepsy as part of an evaluation for epilepsy surgery. His history was significant for herpes meningitis at age 4 months. At that time, he presented to an outside hospital with fever for three days, with acyclovir treatment beginning on day 4 of his 40-day hospital course. He later developed infantile spasms and ultimately a mixed seizure disorder. Video electroencephalogram showed a Lennox-Gastaut-type pattern with frequent right frontotemporal spikes. Imaging studies showed an abnormality in the right frontal operculum. Based on these findings, he underwent a right frontal lobectomy. Neuropathology demonstrated chronic granulomatous inflammation with focal necrosis and mineralizations. Scattered lymphocytes, microglial nodules and nonnecrotizing granulomas were present with multinucleated giant cells. Immunohistochemistry for herpes simplex virus showed focal immunoreactivity. After undergoing acyclovir therapy, he returned to baseline with decreased seizure frequency. This rare form of herpes encephalitis has only been reported in children, but the initial presentation of meningitis and the approximate 10-year-time interval in this case are unusual.

Primary central nervous system angiosarcoma: two case reports.

INTRODUCTION: Primary angiosarcoma of the brain is extremely rare; only 15 cases have been reported in adults over the last 25 years. CASE PRESENTATIONS: We describe two cases of primary angiosarcoma of the brain that are well characterized by imaging, histopathology, and immunohistochemistry. Case 1: our first patient was a 35-year-old woman who developed exophthalmos. Subtotal resection of a left extra-axial retro-orbital mass was performed. Case 2: our second patient was a 47-year-old man who presented to our facility with acute visual loss, word-finding difficulty and subtle memory loss. A heterogeneously-enhancing left sphenoid wing mass was removed. We also review the literature aiming at developing a rational approach to diagnosis and treatment, given the rarity of this entity. CONCLUSIONS: Gross total resection is the standard of care for primary angiosarcoma of the brain. Adjuvant radiation and chemotherapy are playing increasingly recognized roles in the therapy of these rare tumors.

Man with posterior fossa tumors 15 years apart.

A 48-year-old man with a history of hypertension, peripheral vascular disease and a 50-pack-year history of smoking presented with new onset vertigo, tinnitus, diplopia and ataxia in January 1978. CT scan showed a radiolucent defect in the left cerebellar hemisphere with a possible mural nodule. In ensuing months, he experienced worsening symptoms with a corresponding increase in lesion size on re-imaging. Months later, a left posterior fossa craniotomy was performed and revealed a single cystic lesion containing copious amounts of straw-colored fluid and a single mural nodule in the inferior portion of the cyst. Following resection, he was followed clinically until 1985 at which time follow-up was discontinued. He did well until January 1993 when he presented with progressively worsening episodic headaches and retro-orbital pressure. Subsequent MRIs of the brain and spine (February 1993, March 1993) showed multiple lesions along the neuraxis involving the superficial brain parenchyma, leptomeninges, and dura. Despite therapy, his condition progressively declined until he succumbed. A brain-only autopsy revealed numerous small tumor nodules involving the base of the brain over both frontal and temporal lobes, midbrain, pons, right optic nerve, pituitary fossa, and the base of the skull. Pathologic evaluation revealed metastatic hemangioblastoma. Metastatic hemangioblastoma is a rare entity, with only a few reported cases in the literature to date.

Toluene optic neurotoxicity: magnetic resonance imaging and pathologic features.

Toluene, a colorless liquid found in glues, paints, and industrial products, is lipid soluble and rapidly absorbed by the lipid-rich central nervous system. Prolonged exposure through occupation or purposeful inhalation may lead to neurologic abnormalities. Two men presented with multifocal central nervous system defects and bilateral optic neuropathy of unclear etiology. After numerous diagnostic tests, including brain magnetic resonance imaging, lumbar puncture, hematologic studies, and in one patient a brain biopsy, chronic inhalation of toluene was found to be the cause. Timely diagnosis is important because patients may experience improvement in neurologic and ocular manifestations with cessation of exposure, whereas continued inhalant abuse or exposure can result in permanent loss of neurologic function.

Extramedullary hematopoiesis: an unusual finding in subdural hematomas.

We present a case of a 59-year-old man who was found to have clusters of hyperchromatic, small, round nucleated cells within a subdural hematoma removed after a skull fracture. Immunohistochemistry study confirmed that the cells were hematopoietic components predominantly composed of normoblasts. In this paper, we describe the clinical and pathological findings. A brief review of published information on extramedullary hematopoiesis in subdural hematoma and the mechanisms of pathogenesis are also discussed. While extramedullary hematopoiesis is seen anecdotally by neuropathologists in chronic subdural hematomas, only a few cases are documented in the literature. Furthermore, extramedullary hematopoiesis in subdural hematoma can pose a diagnostic challenge for general pathologists who encounter subdural hematoma evacuations seldom in their surgical pathology practices.

Loss of protein inhibitors of activated STAT-3 expression in glioblastoma multiforme tumors: implications for STAT-3 activation and gene expression.

PURPOSE: STATs activate transcription in response to numerous cytokines, controlling proliferation, gene expression, and apoptosis. Aberrant activation of STAT proteins, particularly STAT-3, is implicated in the pathogenesis of many cancers, including GBM, by promoting cell cycle progression, stimulating angiogenesis, and impairing tumor immune surveillance. Little is known about the endogenous STAT inhibitors, the PIAS proteins, in human malignancies. The objective of this study was to examine the expression of STAT-3 and its negative regulator, PIAS3, in human tissue samples from control and GBM brains. EXPERIMENTAL DESIGN: Control and GBM human tissues were analyzed by immunoblotting and immunohistochemistry to determine the activation status of STAT-3 and expression of the PIAS3 protein. The functional consequence of PIAS3 inhibition by small interfering RNA or PIAS3 overexpression in GBM cells was determined by examining cell proliferation, STAT-3 transcriptional activity, and STAT-3 target gene expression. This was accomplished using [(3)H]TdR incorporation, STAT-3 dominant-negative constructs, reverse transcription-PCR, and immunoblotting. RESULTS AND CONCLUSIONS: STAT-3 activation, as assessed by tyrosine and serine phosphorylation, was elevated in GBM tissue compared with control tissue. Interestingly, we observed expression of PIAS3 in control tissue, whereas PIAS3 protein expression in GBM tissue was greatly reduced. Inhibition of PIAS3 resulted in enhanced glioblastoma cellular proliferation. Conversely, PIAS3 overexpression inhibited STAT-3 transcriptional activity, expression of STAT-3-regulated genes, and cell proliferation. We propose that the loss of PIAS3 in GBM contributes to enhanced STAT-3 transcriptional activity and subsequent cell proliferation.

Central nervous system infections in transplant recipients by Cladophialophora bantiana.

Cladophialophora bantiana, a dematiaceous fungus, is an uncommon pathogenic organism originally thought to more commonly affect immunocompetent patients. Increasing numbers of reports, however, describe the organism affecting immunocompromised patients. Like all dematiaceous fungi, Cladophialophora can be recognized in histopathologic sections by the golden-brown coloration in the walls of the hyphae. Of all the dematiaceous fungi, Cladophialophora bantiana demonstrates the most neurotropism, which is responsible for increasing recognition of this fungus as the causative agent in brain abscesses in transplant patients. We describe one patient with a liver transplant and another with a double lung transplant, both of whom developed cerebral abscesses caused by this organism, and review the reported literature.

A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas.

Reovirus is an oncolytic virus with activity in in vivo models of malignant gliomas (MGs). The primary aims were to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of intratumoral administration of reovirus in patients with recurrent MGs. Response, survival, and time to progression (TTP) were secondary aims. Patients were adults, had Karnofsky Performance score > or = 60, received prior radiotherapy with or without chemotherapy, and had up to the third recurrence of MG. Reovirus was administered intratumorally stereotactically at 1 x 10(7), 1 x 10(8), or 1 x 10(9) tissue culture infectious dose 50 (TCID50) in a volume of 0.9 ml. Twelve patients were treated at three dose levels (3, 6, and 3 patients, respectively). Seven were men, median Karnofsky Performance score was 80, and median age was 53.5 years. There were no grade III or IV adverse events (AEs) definitely or probably related to treatment. Ten patients had tumor progression, one had stabilization, and one was not evaluable for response. Median survival was 21 weeks (range, 6-234), and one is alive 54 months after treatment. Median TTP was 4.3 weeks (range, 2.6-39). An MTD was not reached. The intratumoral administration of the genetically unmodified reovirus was well tolerated using these doses and schedule, in patients with recurrent MG.

Primary Ewing sarcoma of the brain: a case report and literature review.

Ewing sarcoma, along with peripheral primitive neuroectodermal tumor, belongs to a tumor family that shares clinicopathologic and molecular genetic features, including the characteristic chromosomal translocation that results in the fusion of the EWS gene on 22q12 to either the FLI1 gene on 11q24 or other Ets family transcription factor gene, such as the ERG gene on 21q22. In contrast, such translocations are not found in central primitive neuroectodermal tumors (cPNETs), such as medulloblastoma and supratentorial PNET. Ewing sarcoma has only rarely been noted to primarily involve the central nervous system-extraosseous Ewing sarcoma (CNS-EES). We report a case of a 7-year-old girl with an anterior cranial fossa mass. Pathology showed a primitive small blue cell tumor with focal Homer Wright rosette formation. The positive membranous immunostaining for CD99 and the EWS-FLI1 fusion demonstrated by fluorescence in situ hybridization studies confirmed the diagnosis of CNS-EES. Although CNS-EES may look identical to cPNETs, these tumors differ in histogenesis, molecular characteristics, and clinical behavior. Demonstration of characteristic translocations by molecular studies differentiates CNS-EES from cPNET and help clinicians make informed decisions regarding therapy.

1p/19q chromosome deletions in metastatic oligodendroglioma.

Extracranial metastasis of primary brain tumors is a rare phenomenon. Of the few cases reported of metastatic oligodendroglioma, only two have evaluated genetic alterations, specifically deletions of chromosomes 1p and 19q. Herein, we report two additional patients with metastatic anaplastic oligodendroglioma to bone, both followed until death. All available pathology specimens were reviewed and genetic analysis was performed in one of the cases. Although the bone metastasis was non-informative, the primary intracranial tumor revealed codeletions of the 1p and 19q chromosomal arms, commonly recognized as the genetically favorable profile of oligodendrogliomas. Both patients died of complications related to their systemic disease and did not have any radiologic evidence of intracranial progression at the time of their last MRI studies. Along with the reported literature, our data suggest that despite their generally favorable behavioral profiles, oligodendroglial tumors with 1p/19q deletions may be more prone to metastasis as they progress. Genetic analysis serves a valuable ancillary role in the diagnostic workup of such cases.

Efficacy and safety evaluation of human reovirus type 3 in immunocompetent animals: racine and nonhuman primates.

PURPOSE: Human reovirus type 3 has been proposed to kill cancer cells with an activated Ras signaling pathway. The purpose of this study was to investigate the efficacy of reovirus in immunocompetent glioma animal models and safety/toxicity in immunocompetent animals, including nonhuman primates. EXPERIMENTAL DESIGN: Racine glioma cells 9L and RG2 were implanted s.c. or intracranially in Fisher 344 rats with or without reovirus antibodies, followed by treatment of reovirus. To study whether reovirus kills contralateral tumors in the brain and to determine viral distribution, we established an in situ dual tumor model followed by reovirus intratumoral inoculation only into the ipsilateral tumor. To evaluate neurotoxicity/safety of reovirus, Cynomolgus monkeys and immunocompetent rats were given intracranially with reovirus, and pathological examination and/or behavioral studies were done. Viral shedding and clinical biochemistry were systematically studied in monkeys. RESULTS: Intratumorally given reovirus significantly suppressed the growth of both s.c. and intracranially tumors and significantly prolonged survival. The presence of reovirus-neutralizing antibodies did not abort the reovirus' antitumor effect. Reovirus inhibited glioma growth intracranially in the ipsilateral but not the contralateral tumors; viral load in ipsilateral tumors was 15 to 330-fold higher than the contralateral tumors. No encephalitis or behavioral abnormalities were found in monkeys and rats given reovirus intracranially. No treatment-related clinical biochemistry changes or diffuse histopathological abnormality were found in monkeys inoculated intracranially with Good Manufacturing Practice prepared reovirus. Microscopic changes were confined to the region of viral inoculation and were dose related, suggesting reovirus intracranially was well tolerated in nonhuman primates. CONCLUSIONS: These data show the efficacy and safety of reovirus when it is used in the treatment of gliomas in immunocompetent hosts. Inoculation of reovirus into the brain of nonhuman primates did not produce significant toxicities.

Suprasellar lymphoid hyperplasia presenting with diabetes insipidus and hypogonadism.

We report a pediatric patient who presented with hypogonadism and diabetes insipidus. Further evaluation revealed hypothyroidism. MRI of the brain revealed a suprasellar mass. Following frontal craniotomy for mass biopsy, histological analysis of the mass revealed benign lymphoid hyperplasia. The patient has had no progression of his mass or symptoms at most recent follow-up (10 months). We review this unusual case and other similar conditions. We believe this to be the first reported case of lymphoid hyperplasia without malignant cells of the suprasellar region.