Intracranial melanotic schwannomas: a rare variant with unusual adherent features.

Intracranial melanotic schwannomas (IMSch) are extremely rare nerve sheath tumors with features of Schwann cells that produce melanin. After a thorough review of the available literature since 1967, we report not only the 20th case of IMSch but a comprehensive modern-era analysis of radiographic and histological key-points to be considered when diagnosing and treating patients with this rare known entity. This is the case of a 43 years-old woman who presented with severe headaches 9 years ago (2008). At that time, MRI of the brain showed a 1.5 × 1.4 cm lesion at the level of the left cerebellar peduncle without any evidence of edema, mass effect or hydrocephalus. Given that the patient was neurologically intact, a conservative management with serial MRIs was recommended. Patient stopped following up due to the absence of symptoms. Over the course of the past year, patient noted mild left sided hearing loss and facial weakness, as well as some balance instability that progressed over the last 3 months. Given the presentation and progression of these signs and symptoms, a new MRI was performed in which considerable growth of the lesion was identified, measuring 2.5 × 2.8 × 2.6 cm with mass effect on the pons and the inferior fourth ventricle. She underwent a far lateral approach without a C1 hemilaminectomy for the resection of this lesion. Final pathology was consistent with a non-psammomatous melanotic schwannoma (NPMS) with areas of necrosis. Besides this case, only two other cases of IMSch with findings of necrosis have been reported in the literature, all of them reporting a subtotal resection. Evaluation of all previously reported cases of IMSch shows a male prevalence with a 1.6:1 male to female ratio. IMSch is radiographically T2 hypointense and can be differentiated from Schwannomas that are classically T2 hyperintense. In this case, only a subtotal resection was feasible due to the tumor's overwhelming inherent attachment to vital structures such as cranial nerves (CN), brainstem, and vasculature. While MSch is considered histologically benign, several factors including localization, surrounding structures, the rate of growth, tumor volume resection and histological necrosis should be considered in determining prognosis and further adjuvant treatment planning.

Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization.

PTEN is a PIP3 phosphatase that antagonizes oncogenic PI3-kinase signalling. Due to its critical role in suppressing the potent signalling pathway, it is one of the most mutated tumour suppressors, especially in brain tumours. It is generally thought that PTEN deficiencies predominantly result from either loss of expression or enzymatic activity. By analysing PTEN in malignant glioblastoma primary cells derived from 16 of our patients, we report mutations that block localization of PTEN at the plasma membrane and nucleus without affecting lipid phosphatase activity. Cellular and biochemical analyses as well as structural modelling revealed that two mutations disrupt intramolecular interaction of PTEN and open its conformation, enhancing polyubiquitination of PTEN and decreasing protein stability. Moreover, promoting mono-ubiquitination increases protein stability and nuclear localization of mutant PTEN. Thus, our findings provide a molecular mechanism for cancer-associated PTEN defects and may lead to a brain cancer treatment that targets PTEN mono-ubiquitination.

Epigenetic modulation of a miR-296-5p:HMGA1 axis regulates Sox2 expression and glioblastoma stem cells.

Solid malignancies contain subsets of multipotent cells that grow as spheres and efficiently propagate tumors in xenograft models, reflecting a stem-like, self-renewing and tumor-propagating phenotype. These cancer 'stem cells (SCs)' have been shown to maintain tumor growth, contribute to resistance and drive tumor recurrence. Cancer cell stemness is dynamically influenced by epigenetic mechanisms and differentially regulated coding and noncoding RNAs. How these mechanisms specifically contribute to the generation and/or maintenance of cancer SCs remains unclear. This study identifies a novel epigenetically regulated circuit that integrates microRNA, chromatin remodeling and the reprogramming transcription factor Sox2 to regulate glioblastoma (GBM)-propagating SCs. We show that miR-296-5p expression is repressed in a DNA methylation-dependent manner under conditions that promote GBM cell stemness and that miR-296-5p inhibits GBM cell stemness and their capacity to self-renew as spheres and propagate glioma xenografts in vivo. We show that the chromatin remodeling protein HMGA1 functions as a downstream effector of these biological responses to miR-296-5p and regulates Sox2 expression, a master driver of cell stemness, by modifying chromatin architecture at the Sox2 promoter. These results show for the first time that miR-296-5p inhibits transcriptional mechanisms that support GBM SCs and identify a miR-296-5p:HMGA1:Sox2 axis as a novel regulator of GBM SCs and candidate pathway for targeting therapies directed at depleting tumors of their tumor-propagating stem cell subsets.

PAR1 inhibition suppresses the self-renewal and growth of A2B5-defined glioma progenitor cells and their derived gliomas in vivo.

Glioblastoma (GBM) remains the most common and lethal intracranial tumor. In a comparison of gene expression by A2B5-defined tumor-initiating progenitor cells (TPCs) to glial progenitor cells derived from normal adult human brain, we found that the F2R gene encoding PAR1 was differentially overexpressed by A2B5-sorted TPCs isolated from gliomas at all stages of malignant development. In this study, we asked if PAR1 is causally associated with glioma progression. Lentiviral knockdown of PAR1 inhibited the expansion and self-renewal of human GBM-derived A2B5(+) TPCs in vitro, while pharmacological inhibition of PAR 1 similarly slowed both the growth and migration of A2B5(+) TPCs in culture. In addition, PAR1 silencing potently suppressed tumor expansion in vivo, and significantly prolonged the survival of mice following intracranial transplantation of human TPCs. These data strongly suggest the importance of PAR1 to the self-renewal and tumorigenicity of A2B5-defined glioma TPCs; as such, the abrogation of PAR1-dependent signaling pathways may prove a promising strategy for gliomas.

DNMT-dependent suppression of microRNA regulates the induction of GBM tumor-propagating phenotype by Oct4 and Sox2.

Cancer stem-like cells represent poorly differentiated multipotent tumor-propagating cells that contribute disproportionately to therapeutic resistance and tumor recurrence. Transcriptional mechanisms that control the phenotypic conversion of tumor cells lacking tumor-propagating potential to tumor-propagating stem-like cells remain obscure. Here we show that the reprogramming transcription factors Oct4 and Sox2 induce glioblastoma cells to become stem-like and tumor-propagating via a mechanism involving direct DNA methyl transferase (DNMT) promoter transactivation, resulting in global DNA methylation- and DNMT-dependent downregulation of multiple microRNAs (miRNAs). We show that one such downregulated miRNA, miRNA-148a, inhibits glioblastoma cell stem-like properties and tumor-propagating potential. This study identifies a novel and targetable molecular circuit by which glioma cell stemness and tumor-propagating capacity are regulated.

Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer.

Adult human adipose-derived mesenchymal stem cells (hAMSCs) are multipotent cells, which are abundant, easily collected, and bypass the ethical concerns that plague embryonic stem cells. Their utility and accessibility have led to the rapid development of clinical investigations to explore their autologous and allogeneic cellular-based regenerative potential, tissue preservation capabilities, anti-inflammatory properties, and anticancer properties, among others. hAMSCs are typically cultured under ambient conditions with 21% oxygen. However, physiologically, hAMSCs exist in an environment of much lower oxygen tension. Furthermore, hAMSCs cultured in standard conditions have shown limited proliferative and migratory capabilities, as well as limited viability. This study investigated the effects hypoxic culture conditions have on primary intraoperatively derived hAMSCs. hAMSCs cultured under hypoxia (hAMSCs-H) remained multipotent, capable of differentiation into osteogenic, chondrogenic, and adipogenic lineages. In addition, hAMSCs-H grew faster and exhibited less cell death. Furthermore, hAMSCs-H had greater motility than normoxia-cultured hAMSCs and exhibited greater homing ability to glioblastoma (GBM) derived from brain tumor-initiating cells from our patients in vitro and in vivo. Importantly, hAMSCs-H did not transform into tumor-associated fibroblasts in vitro and were not tumorigenic in vivo. Rather, hAMSCs-H promoted the differentiation of brain cancer cells in vitro and in vivo. These findings suggest an alternative culturing technique that can enhance the function of hAMSCs, which may be necessary for their use in the treatment of various pathologies including stroke, myocardial infarction, amyotrophic lateral sclerosis, and GBM.

Immunological regulation of neurogenic niches in the adult brain.

In mammals, neurogenesis and oligodendrogenesis are germinal processes that occur in the adult brain throughout life. The subventricular zone (SVZ) and subgranular zone (SGZ) are the main neurogenic regions in the adult brain. Therein, resides a subpopulation of astrocytes that act as neural stem cells (NSCs). Increasing evidence indicates that pro-inflammatory and other immunological mediators are important regulators of neural precursors into the SVZ and the SGZ. There are a number of inflammatory cytokines that regulate the function of NSCs. Some of the most studied include: interleukin-1, interleukin-6, tumor necrosis factor alpha, insulin-like growth factor-1, growth-regulated oncogene-alpha, leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha. This plethora of immunological mediators can control the migration, proliferation, quiescence, cell-fate choices and survival of NSCs and their progeny. Thus, systemic or local inflammatory processes represent important regulators of germinal niches in the adult brain. In this review, we summarized the current evidence regarding the effects of pro-inflammatory cytokines involved in the regulation of adult NSCs under in vitro and in vivo conditions. Additionally, we described the role of proinflammatory cytokines in neurodegenerative diseases and some therapeutical approaches for the immunomodulation of neural progenitor cells.

Neurotransplantation: lux et veritas, fiction or reality?

Neurotransplantation remains a much-debated frontier in contemporary neurosurgery and neuroscience, with roots dating to the late 19th century. Contemporary applications are far-reaching, and ongoing laboratory research and clinical trials seek to define the mechanisms at play in neurotransplant engraftment and growth, while advancing the field forward into the 21st century. Neural transplantation therapy remains an attractive idea for treating central nervous system (CNS) and peripheral nervous system (PNS) pathologies. Phase I and phase II clinical trials assessing safety and efficacy are currently underway for various disorders. The remainder of this review will focus on ongoing clinical trials and more recent research advances involving neural transplantation therapy for neuronal death, axonal injury, peripheral nerve lesions, and cancer. The field of neural transplantation, while promising, is not without ethical and scientific dilemmas; this review will conclude with a discussion of the challenges researchers and clinicians face as the field of neural transplantation moves forward.

Minimally invasive trans-portal resection of deep intracranial lesions.

BACKGROUND: The surgical management of deep intra-axial lesions still requires microsurgical approaches that utilize retraction of deep white matter to obtain adequate visualization. We report our experience with a new tubular retractor system, designed specifically for intracranial applications, linked with frameless neuronavigation for a cohort of intraventricular and deep intra-axial tumors. METHODS: The ViewSite Brain Access System (Vycor, Inc) was used in a series of 9 adult and pediatric patients with a variety of pathologies. Histological diagnoses either resected or biopsied with the system included: colloid cyst, DNET, papillary pineal tumor, anaplastic astrocytoma, toxoplasmosis and lymphoma. The locations of the lesions approached include: lateral ventricle, basal ganglia, pulvinar/posterior thalamus and insular cortex. Post-operative imaging was assessed to determine extent of resection and extent of white matter damage along the surgical trajectory (based on T (2)/FLAIR and diffusion restriction/ADC signal). RESULTS: Satisfactory resection or biopsy was obtained in all patients. Radiographic analysis demonstrated evidence of white matter damage along the surgical trajectory in one patient. None of the patients experienced neurological deficits as a result of white matter retraction/manipulation. CONCLUSION: Based on a retrospective review of our experience, we feel that this access system, when used in conjunction with frameless neuronavigational systems, provides adequate visualization for tumor resection while permitting the use of standard microsurgical techniques through minimally invasive craniotomies. Our initial data indicate that this system may minimize white matter injury, but further studies are necessary.

Localized CT-guided irradiation inhibits neurogenesis in specific regions of the adult mouse brain.

Radiation is used in the study of neurogenesis in the adult mouse both as a model for patients undergoing radiation therapy for CNS malignancies and as a tool to interrupt neurogenesis. We describe the use of a dedicated CT-guided precision device to irradiate specific sub-regions of the adult mouse brain. Improved CT visualization was accomplished with intrathecal injection of iodinated contrast agent, which enhances the lateral ventricles. T2-weighted MRI images were also used for target localization. Visualization of delivered beams (10 Gy) in tissue was accomplished with immunohistochemical staining for the protein γ-H2AX, a marker of DNA double-strand breaks. γ-H2AX stains showed that the lateral ventricle wall could be targeted with an accuracy of 0.19 mm (n = 10). In the hippocampus, γ-H2AX staining showed that the dentate gyrus can be irradiated unilaterally with a localized arc treatment. This resulted in a significant decrease of proliferative neural progenitor cells as measured by Ki-67 staining (P < 0.001) while leaving the contralateral side intact. Two months after localized irradiation, neurogenesis was significantly inhibited in the irradiated region as seen with EdU/NeuN double labeling (P < 0.001). Localized radiation in the rodent brain is a promising new tool for the study of neurogenesis.

Regulation of glioblastoma stem cells by retinoic acid: role for Notch pathway inhibition.

It is necessary to understand mechanisms by which differentiating agents influence tumor-initiating cancer stem cells. Toward this end, we investigated the cellular and molecular responses of glioblastoma stem-like cells (GBM-SCs) to all-trans retinoic acid (RA). GBM-SCs were grown as non-adherent neurospheres in growth factor supplemented serum-free medium. RA treatment rapidly induced morphology changes, induced growth arrest at G1/G0 to S transition, decreased cyclin D1 expression and increased p27 expression. Immunofluorescence and western blot analysis indicated that RA induced the expression of lineage-specific differentiation markers Tuj1 and GFAP and reduced the expression of neural stem cell markers such as CD133, Msi-1, nestin and Sox-2. RA treatment dramatically decreased neurosphere-forming capacity, inhibited the ability of neurospheres to form colonies in soft agar and inhibited their capacity to propagate subcutaneous and intracranial xenografts. Expression microarray analysis identified ∼350 genes that were altered within 48 h of RA treatment. Affected pathways included retinoid signaling and metabolism, cell-cycle regulation, lineage determination, cell adhesion, cell-matrix interaction and cytoskeleton remodeling. Notch signaling was the most prominent of these RA-responsive pathways. Notch pathway downregulation was confirmed based on the downregulation of HES and HEY family members. Constitutive activation of Notch signaling with the Notch intracellular domain rescued GBM neurospheres from the RA-induced differentiation and stem cell depletion. Our findings identify mechanisms by which RA targets GBM-derived stem-like tumor-initiating cells and novel targets applicable to differentiation therapies for glioblastoma.

"Colossal" breakthrough: the callosal puncture as a precursor to third ventriculostomy.

BACKGROUND: In 1908, Anton and von Bramann proposed the Balkenstich method, a corpus callosum puncture which created a communication between the ventricle and subarachnoid space. This method offered the benefit of providing continuous CSF diversion without the implantation of cannula or other shunting devices, yet it received only slight reference in the literature of the time. It remained a novel and perhaps underutilized approach at the time Cushing began expanding his neurosurgical practice at the Johns Hopkins Hospital. MATERIALS AND METHODS: Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical records of the Johns Hopkins Hospital for the period 1896-1912 were reviewed. Patients operated upon by Harvey Cushing were selected. RESULTS: 7 patients underwent puncture of the corpus callosum for treatment of hydrocephalus. 6 patients were treated for obstructive hydrocephalus secondary to presumed intracranial lesions. 1 patient was treated for congenital hydrocephalus. CONCLUSION: The series reported here documents Cushing's early use of the corpus callosum puncture to divert CSF in patients with obstructive hydrocephalus secondary to intracranial tumors, as well as an attempt to use the procedure in a pediatric patient with congenital hydrocephalus. Notably, 3 patients developed new onset left-sided weakness post-operatively, possibly due to retraction injury upon the supplementary motor intra-operative manipulations.

FACT-MNG: tumor site specific web-based outcome instrument for meningioma patients.

To formulate Functional Assessment of Cancer Therapy-Meningioma (FACT-MNG), a web-based tumor site-specific outcome instrument for assessing intracranial meningioma patients following surgical resection or stereotactic radiosurgery. We surveyed the relevant literature available on intracranial meningioma surgery and subsequent outcomes (38 papers), making note of which, if any, QOL/outcome instruments were utilized. None of the surgveyed papers included QOL assessment specific to tumor site. We subsequently developed questions that were relevant to the signs and symptoms that characterize each of 11 intracranial meningioma sites, and incorporated them into a modified combination of the Functional Assessment of Cancer Therapy-Brain (FACT-BR) and SF36 outcome instruments, thereby creating a new tumor site-specific outcome instrument, FACT-MNG. With outcomes analysis of surgical and radiosurgical treatments becoming more important, measures of the adequacy and success of treatment are needed. FACT-MNG represents a first effort to formalize such an instrument for meningioma patients. Questions specific to tumor site will allow surgeons to better assess specific quality of life issues not addressed in the past by more general questionnaires.

The supraorbital craniotomy for access to the skull base and intraaxial lesions: a technique in evolution.

INTRODUCTION: The supraorbital craniotomy was initially described as a minimally invasive means to target extra-axial lesions in the anterior cranial fossa and sellar/parasellar region. Since its initial description, various modifications have been described. We report our recent experience with this approach (and its modifications) for not only extra-axial but also intra-axial neoplastic pathology. METHODS: Based on patient pathology and anatomic considerations, one of two approaches was performed: supraorbital craniotomy through an eyebrow incision or a combined orbital osteotomy and supraorbital craniotomy through an eyelid incision. RESULTS: This technique was performed on twenty-eight consecutive patients. Intra-axial pathology ranged from anaplastic astrocytoma to metastasis while extra-axial lesions included meningiomas and skull-based metastases. Excellent lesion resection was achieved in the majority of patients. Complications were infection (2 patients) and CSF leak. DISCUSSION: The supraorbital craniotomy and its modifications provide an ideal anterior subfrontal approach through which a wide variety of pathology can be approached. This technique has particular considerations in comparison to traditional cranial base approaches that must be taken into account before it is utilized.

The tandem bypass: subclavian artery-to-middle cerebral artery bypass with dacron and saphenous vein grafts. Technical case report.

BACKGROUND: Fusiform or dolichoectatic intracranial aneurysms often cannot be managed with conventional surgical or endovascular techniques, and instead require trapping and revascularization techniques. On rare occasions in elderly patients, extracranial sites used for anastomosing the bypass have been previously repaired with synthetic vascular prostheses. This circumstance in an elderly subarachnoid hemorrhage patient led to a novel bypass procedure, the tandem bypass: a long extracranial-to-intracranial bypass with two grafts of different materials assembled in series. CASE DESCRIPTION: A 71-year-old man with carotid artery atherosclerotic disease and a previous vascular reconstruction (subclavian artery-to-internal carotid artery Dacron interposition graft) presented with a subarachnoid hemorrhage from a dolichoectatic supraclinoid ICA aneurysm. The aneurysm was treated with trapping and distal revascularization. The final construct was a subclavian artery-to-middle cerebral artery bypass, with the graft being the previous Dacron prosthesis and a long saphenous vein. The vein graft was anastomosed end-to-side to the Dacron graft proximally, and end-to side to the middle cerebral artery distally. Subsequently, inflow to the aneurysm was occluded with clips on the Dacron graft beyond the proximal anastomosis of the vein graft, and outflow from the aneurysm was occluded with clips on the supraclinoid ICA. CONCLUSIONS: The tandem bypass, which uses prosthetic graft material and saphenous vein in succession, is a technically straightforward technique in patients who need extracranial-to-intracranial bypasses and who also have pre-existing carotid reconstructions or lack sufficient saphenous vein to complete a long bypass.

Conus perimedullary arteriovenous fistula with intracranial drainage: case report.

OBJECTIVE AND IMPORTANCE: Perimedullary arteriovenous fistulae (AVFs) do not commonly present with subarachnoid hemorrhage or intracranial venous drainage causing neurological symptoms. We present a case with both of these features. The patient was inadvertently treated for an unruptured intracranial aneurysm before his true problem was recognized. CLINICAL PRESENTATION: A 65-year-old man presented with sudden-onset lower-extremity weakness, diplopia, nausea, and dysarthria on the day of admission. A lumbar puncture documented subarachnoid hemorrhage, and imaging studies revealed a left middle cerebral artery aneurysm. It was noted during surgery that this aneurysm was unruptured, and the patient did not exhibit improvement after surgery. INTERVENTION: Spinal angiography demonstrated a spinal perimedullary AVF feeding from the left T12 radicular artery; venous drainage extended rostrally into the posterior fossa venous system. The AVF was surgically occluded via a posterior laminectomy at the level of the AVF. After surgery, the patient's symptoms began to abate. CONCLUSION: Conus perimedullary AVFs can have venous drainage that extends as far as intracranial veins, which can lead to confusing clinical findings because the symptoms may suggest an intracranial process, although the lesion is in the spine. Surgeons must be aware of this confusing presentation.

Quality of life following surgery for intracranial meningiomas at Brigham and Women's Hospital: a study of 164 patients using a modification of the functional assessment of cancer therapy-brain questionnaire.

The objective of this study was to determine the subjectively reported quality of life (QOL) of patients with meningiomas surgically treated. Demographic, medical and outcomes data on 164 patients were retrospectively analyzed with the use of the Brain Tumor Center database at the Brigham and Women's Hospital, Boston, MA. The patients were contacted via a telephone survey and were asked 26 standardized QOL questions based on a modification of the validated Functional Assessment of Cancer Therapy-Brain (FACT-BR) Study, which used only questions adjuvant to brain tumor patients. The patients' ages ranged from 23 to 87 years. The mean follow-up time after intracranial surgery was 33 months and median follow-up time was 28 months, with a range of 0 to 165 months. Of those 164 patients still living, 95% (155) participated in the telephone survey. 80% reported being satisfied with their post-treatment quality of life; 86% reported that they could write, read, drive and return to work at their pre-morbid level of functioning; 87% described themselves as 'independent' and able to act on their own initiatives. Our study found a high level of satisfaction for QOL in patients who have undergone surgery for intracranial meningiomas. Patients, by their own report, are able to lead independent, personally satisfying, meaningful and productive lives. This provides useful information to share with patients in discussions regarding surgical treatment of these lesions.

Frameless stereotactic neurosurgery using intraoperative magnetic resonance imaging: stereotactic brain biopsy.

OBJECTIVE: To assess the application accuracy of intraoperative magnetic resonance imaging for frameless stereotactic surgery, and to evaluate the performance of intraoperative magnetic resonance imaging for the brain biopsy, a standard stereotactic procedure. METHODS: A series of spatial coordinate and phantom experiments were performed to analyze the application accuracy of the system. A prospective analysis of 68 consecutive patients undergoing stereotactic brain biopsy was then performed. RESULTS: The spatial coordinate experiments revealed a mean overall error in acquisition of 0.2 mm. The phantom experiments demonstrated a 1:1 correlation between the magnetic resonance image of a stereotactically guided probe and its relationship to a target and the actual relationship of the probe and target. Sixty-eight brain biopsies were successfully performed in all intracranial compartments except the sella. The radiographic abnormality was localized successfully in all patients (100%). Sixty-six (97.1%) of the biopsies yielded diagnostic tissue. Two biopsies (2.9%) were complicated by intraparenchymal hemorrhage. One expanding temporal lobe hemorrhage was evacuated by immediate craniotomy in the magnet with no postoperative sequelae. A deep hemorrhage from a lymphoma was managed conservatively with interval resolution of symptoms. There were no infections. There was no perioperative mortality. CONCLUSION: Intraoperative magnetic resonance imaging allows excellent target localization, provides true real-time imaging to account for anatomic changes during surgery, and permits intraoperative confirmation that the biopsy needle has reached the targeted lesion. Immediate postoperative imaging in the operating room allows assessment of adverse events and the potential for immediate management of hemorrhagic complications.

Solitary sciatic nerve lymphoma as an initial manifestation of diffuse neurolymphomatosis. Case report and review of the literature.

Solitary peripheral nerve lymphomas are exceedingly rare primary manifestations of diffuse peripheral nervous system or central nervous system (CNS) lymphomatosis. A 52-year-old man presented with progressive weakness in gastrocnemius and anterior tibial muscle function, which was associated with radiating pain in the right leg. Magnetic resonance imaging studies revealed a solitary fusiform tumor, extending from the sciatic nerve, at the level of the lesser trochanter of the femur, into the posterior tibial nerve below the popliteal fossa. Intraoperative gross examination found that the tumor diffusely expanded the nerve, but did not extend from or into surrounding muscle or tendons. The final histological diagnosis was a solitary extranodal lymphoma (Burkittlike high-grade B-cell lymphoma). Postoperative staging did not reveal evidence of lymphomatous involvement of other organs, but additional chemo- and radiotherapies were administered. Four months after the surgical biopsy, the patient presented with a right facial nerve palsy. The results of cytological examination of cerebrospinal fluid were positive for the presence of atypical lymphocytes, which was consistent with apparently progressive neurolymphomatosis; however, the results of radiological studies were negative for systemic progression. The patient underwent intrathecal chemotherapy followed by systemic myelosuppressive chemotherapy with bone marrow rescue, but died of respiratory failure while still receiving treatment. Postmortem examination revealed extensive lymphomatosis in the peripheral nerves and spinal nerve roots without evidence of cranial nerve, CNS, or other organ system involvement. The aggressive biological characteristics of these tumors, their management, and pertinent literature are reviewed.