Rhabdomyosarcomas are oncogene addicted to the activation of AVIL.

Rhabdomyosarcoma (RMS) is one of the most common pediatric soft-tissue cancer. Previously, we discovered a gene fusion, MARS-AVIL formed by chromosomal inversion in RMS. Suspecting that forming a fusion with a housekeeping gene may be one of the mechanisms to dysregulate an oncogene, we investigated AVIL expression and its role in RMS. We first showed that MARS-AVIL translates into an in-frame fusion protein, which is critical for RMS cell tumorigenesis. Besides forming a gene fusion with the housekeeping gene, MARS, the AVIL locus is often amplified, and its RNA and protein expression are overexpressed in the majority of RMSs. Tumors with AVIL dysregulation exhibit evidence of oncogene addiction: Silencing MARS-AVIL in cells harboring the fusion, or silencing AVIL in cells with AVIL overexpression, nearly eradicated the cells in culture, as well as inhibited in vivo xenograft growth in mice. Conversely, gain-of-function manipulations of AVIL led to increased cell growth and migration, enhanced foci formation in mouse fibroblasts, and most importantly transformed mesenchymal stem cells in vitro and in vivo. Mechanistically, AVIL seems to serve as a converging node functioning upstream of two oncogenic pathways, PAX3-FOXO1 and RAS, thus connecting two types of RMS associated with these pathways. Interestingly, AVIL is overexpressed in other sarcoma cells as well, and its expression correlates with clinical outcomes, with higher levels of AVIL expression being associated with worse prognosis. AVIL is a bona fide oncogene in RMS, and RMS cells are addicted to its activity.

Rosai-Dorfman Disease: A Less Common Cause of Leptomeningeal and Nerve Root Enhancement.

A 46-year-old male experienced progressive neurocognitive decline, weight loss, intermittent headaches, and weakness over 6 months. Magnetic resonance imaging of the brain revealed hydrocephalus and the spinal cord imaging showed diffuse leptomeningeal enhancement with prominent nerve root involvement. Intradural biopsy of lumbar arachnoid tissue found mixed inflammatory infiltrate consisting predominantly of histiocytes, S100 and CD68 positivity, and lymphocytophagocytosis (emperipolesis) consistent with extranodal Rosai-Dorfman disease. Rosai-Dorfman disease, a non-Langerhans cell histocytic disorder, can mimic the appearance of neurosarcoidosis and leptomeningeal carcinomatosis and should remain on the differential of a patient presenting with diffuse leptomeningeal enhancement, a common occurrence on a neurohospitalist service.

A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma.

Glioblastoma is a deadly cancer, with no effective therapies. Better understanding and identification of selective targets are urgently needed. We found that advillin (AVIL) is overexpressed in all the glioblastomas we tested including glioblastoma stem/initiating cells, but hardly detectable in non-neoplastic astrocytes, neural stem cells or normal brain. Glioma patients with increased AVIL expression have a worse prognosis. Silencing AVIL nearly eradicated glioblastoma cells in culture, and dramatically inhibited in vivo xenografts in mice, but had no effect on normal control cells. Conversely, overexpressing AVIL promoted cell proliferation and migration, enabled fibroblasts to escape contact inhibition, and transformed immortalized astrocytes, supporting AVIL being a bona fide oncogene. We provide evidence that the tumorigenic effect of AVIL is partly mediated by FOXM1, which regulates LIN28B, whose expression also correlates with clinical prognosis. AVIL regulates the cytoskeleton through modulating F-actin, while mutants disrupting F-actin binding are defective in its tumorigenic capabilities.

A Rare Case of Pancreatoblastoma with Intracranial Seeding.

BACKGROUND: Pancreatoblastoma is an extremely rare neoplasm that accounts for 0.5% of all pancreatic exocrine tumors. These rare entities typically manifest in the pediatric population but can rarely occur in adults. Systemic seeding has been described before but intracranial metastasis in adults has yet to be described. CASE DESCRIPTION: A 28-year-old woman with a history of pancreatoblastoma that had been in remission for 51 months after treatment with cisplatin, doxorubicin (Adriamycin), and etoposide had presented to the emergency room with chronic recurrent headaches. Conservative management of the headaches failed, which led to a diagnostic workup with magnetic resonance imaging of the brain. Magnetic resonance imaging demonstrated a well-circumscribed solitary cerebellar lesion. Metastatic disease was suspected, and the patient underwent suboccipital craniotomy for tumor resection with adjuvant gamma knife radiosurgery. CONCLUSIONS: Central nervous system seeding of pancreatoblastoma is rare, and the available evidence suggests that the strategy we used could be adequate for treating such occurrences.

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study).

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types.

Diagnostic Efficiency in Digital Pathology: A Comparison of Optical Versus Digital Assessment in 510 Surgical Pathology Cases.

Prior work has shown that digital images and microscopic slides can be interpreted with comparable diagnostic accuracy. Although accuracy has been well-validated, the interpretative time for digital images has scarcely been studied and concerns about efficiency remain a major barrier to adoption. We investigated the efficiency of digital pathology when compared with glass slide interpretation in the diagnosis of surgical pathology biopsy and resection specimens. Slides were pulled from 510 surgical pathology cases from 5 organ systems (gastrointestinal, gynecologic, liver, bladder, and brain). Original diagnoses were independently confirmed by 2 validating pathologists. Diagnostic slides were scanned using the Philips IntelliSite Pathology Solution. Each case was assessed independently on digital and optical by 3 reading pathologists, with a ≥6 week washout period between modalities. Reading pathologists recorded assessment times for each modality; digital times included time to load the case. Diagnostic accuracy was determined based on whether a rendered diagnosis differed significantly from the original diagnosis. Statistical analysis was performed to assess for differences in interpretative times across modalities. All 3 reading pathologists showed comparable diagnostic accuracy across optical and digital modalities (mean major discordance rates with original diagnosis: 4.8% vs. 4.4%, respectively). Mean assessment times ranged from 1.2 to 9.1 seconds slower on digital versus optical. The slowest reader showed a significant learning effect during the course of the study so that digital assessment times decreased over time and were comparable with optical times by the end of the series. Organ site and specimen type did not significantly influence differences in interpretative times. In summary, digital image reading times compare favorably relative to glass slides across a variety of organ systems and specimen types. Mean increase in assessment time is 4 seconds/case. This time can be minimized with experience and may be further balanced by the improved ease of electronic chart access allowed by digital slide viewing, as well as quantitative assessments which can be expedited on digital images.

Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores Dopaminergic Neuron Function in a Rat Parkinson's Disease Model.

Therapies capable of decelerating, or perhaps even halting, neurodegeneration in Parkinson's disease (PD) remain elusive. Clinical trials of PD gene therapy testing the delivery of neurotrophic factors, such as the glial cell-line derived neurotrophic factor (GDNF), have been largely ineffective due to poor vector distribution throughout the diseased regions in the brain. In addition, current delivery strategies involve invasive procedures that obviate the inclusion of early stage patients who are most likely to benefit from GDNF-based gene therapy. Here, we introduce a two-pronged treatment strategy, composed of MR image-guided focused ultrasound (FUS) and brain-penetrating nanoparticles (BPN), that provides widespread but targeted GDNF transgene expression in the brain following systemic administration. MR image-guided FUS allows circulating gene vectors to partition into the brain tissue by noninvasive and transient opening of the blood-brain barrier (BBB) within the areas where FUS is applied. Once beyond the BBB, BPN provide widespread and uniform GDNF expression throughout the targeted brain tissue. After only a single treatment, our strategy led to therapeutically relevant levels of GDNF protein content in the FUS-targeted regions in the striatum of the 6-OHDA-induced rat model of PD, which lasted at least up to 10 weeks. Importantly, our strategy restored both dopamine levels and dopaminergic neuron density and reversed behavioral indicators of PD-associated motor dysfunction with no evidence of local or systemic toxicity. Our combinatorial approach overcomes limitations of current delivery strategies, thereby potentially providing a novel means to treat PD.

Quantitative Analysis of the Cellular Microenvironment of Glioblastoma to Develop Predictive Statistical Models of Overall Survival.

Glioblastomas, the most common primary malignant brain tumors, have a distinct tissue microenvironment. Although non-neoplastic cells contribute to glioblastoma progression, very few quantitative studies have shown the effect of tumor microenvironmental influences on patient survival. We examined relationships of the cellular microenvironment, including astrocytes, microglia, oligodendrocytes, and blood vessels, to survival in glioblastoma patients. Using histological staining and quantitative image analyses, we examined the tumor-associated parenchyma of 33 patients and developed statistical models to predict patient outcomes based on the cellular picture of the tumor parenchyma. We found that blood vessel density correlated with poorer prognosis. To examine the role of adjacent parenchymal versus higher tumor cell density bulk parenchymal tissue, we examined the glial components in these highly variable regions. Comparison of bulk and adjacent astrocytes and microglia in tissue yielded the strongest prediction of survival, with high levels of adjacent astrocytes predicted poor prognosis and high levels of microglia correlated with a better prognosis. These results indicate that parenchymal components predict survival in glioblastoma patients and in particular that the balance between reactive glial populations is important for patient prognosis.

LRP1 expression in microglia is protective during CNS autoimmunity.

Multiple sclerosis is a devastating neurological disorder characterized by the autoimmune destruction of the central nervous system myelin. While T cells are known orchestrators of the immune response leading to MS pathology, the precise contribution of CNS resident and peripheral infiltrating myeloid cells is less well described. Here, we explore the myeloid cell function of Low-density lipoprotein receptor-related protein-1 (LRP1), a scavenger receptor involved in myelin clearance and the inflammatory response, in the context of Multiple sclerosis. Supporting its central role in Multiple sclerosis pathology, we find that LRP1 expression is increased in Multiple sclerosis lesions in comparison to the surrounding healthy tissue. Using two genetic mouse models, we show that deletion of LRP1 in microglia, but not in peripheral macrophages, negatively impacts the progression of experimental autoimmune encephalomyelitis, an animal model of Multiple sclerosis. We further show that the increased disease severity in experimental autoimmune encephalomyelitis is not due to haplodeficiency of the Cx3cr1 locus. At the cellular level, microglia lacking LRP1 adopt a pro-inflammatory phenotype characterized by amoeboid morphology and increased production of the inflammatory mediator TNF-α. We also show that LRP1 functions as a robust inhibitor of NF-kB activation in myeloid cells via a MyD88 dependent pathway, potentially explaining the increase in disease severity observed in mice lacking LRP1 expression in microglia. Taken together, our data suggest that the function of LRP1 in microglia is to keep these cells in an anti-inflammatory and neuroprotective status during inflammatory insult, including experimental autoimmune encephalomyelitis and potentially in Multiple sclerosis.

Culture conditions tailored to the cell of origin are critical for maintaining native properties and tumorigenicity of glioma cells.

BACKGROUND: Cell culture plays a pivotal role in cancer research. However, culture-induced changes in biological properties of tumor cells profoundly affect research reproducibility and translational potential. Establishing culture conditions tailored to the cancer cell of origin could resolve this problem. For glioma research, it has been previously shown that replacing serum with defined growth factors for neural stem cells (NSCs) greatly improved the retention of gene expression profile and tumorigenicity. However, among all molecular subtypes of glioma, our laboratory and others have previously shown that the oligodendrocyte precursor cell (OPC) rather than the NSC serves as the cell of origin for the proneural subtype, raising questions regarding the suitability of NSC-tailored media for culturing proneural glioma cells. METHODS: OPC-originated mouse glioma cells were cultured in conditions for normal OPCs or NSCs, respectively, for multiple passages. Gene expression profiles, morphologies, tumorigenicity, and drug responsiveness of cultured cells were examined in comparison with freshly isolated tumor cells. RESULTS: OPC media-cultured glioma cells maintained tumorigenicity, gene expression profiles, and morphologies similar to freshly isolated tumor cells. In contrast, NSC-media cultured glioma cells gradually lost their OPC features and most tumor-initiating ability and acquired heightened sensitivity to temozolomide. CONCLUSIONS: To improve experimental reproducibility and translational potential of glioma research, it is important to identify the cell of origin, and subsequently apply this knowledge to establish culture conditions that allow the retention of native properties of tumor cells.

Redefining the Prevalence of Dural Involvement in Rosai-Dorfman Disease of the Central Nervous System.

BACKGROUND: Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease, is a rare condition, classically characterized by painless, massive cervical lymphadenopathy. Histologically, the pathognomonic findings include a dense, mixed inflammatory infiltrate with areas of emperipolesis. Albeit infrequent, when Rosai-Dorfman disease affects the central nervous system, it typically manifests as an isolated dural lesion, often mimicking a meningioma. A purely intraparenchymal manifestation of Rosai-Dorfman disease of the brain and spine with absent dural involvement is exceedingly rare. CASE DESCRIPTION: In this report, we describe a 59-year-old woman who underwent surgical excision of an intraparenchymal cerebellar lesion. Histologic analysis of the resected specimen diagnosed isolated Rosai-Dorfman disease with absent systemic involvement. We also provide an updated review of the literature of nondural-based Rosai-Dorfman disease in the central nervous system. CONCLUSIONS: With the recent increase of such reported cases, it becomes imperative that Rosai-Dorfman be considered more than as a dural lesion that may mimic meningioma. Diagnostic and therapeutic challenges surrounding this disease entity are also discussed.

Histiocytic sarcoma of the cavernous sinus: case report and literature review.

Histiocytic sarcoma is a rare malignant neoplasm of hematopoietic origin composed of cells showing morphologic and immunophenotypic evidence of histiocytic differentiation. We describe the 2nd case of primary histiocytic sarcoma of the cavernous sinus/Meckel's cave, and the 8th case involving the CNS. A 61-year-old Caucasian man presented with numbness on the entire left side of his face, shooting pain in the left frontal region, and headaches. Imaging revealed an enhancing extra axial soft tissue mass located in the left cavernous sinus and left Meckel's cave. Diagnosis was established through open biopsy, after failed attempts via CT-guided trans-foramen ovale fine-needle aspiration biopsy and keyhole biopsy. The tumor was composed of large non-cohesive epithelioid cells invading nerves and ganglion cells. Tumor cells were immunopositive for CD68, CD163, and immunonegative for the anaplastic large cell lymphoma marker ALK-1 as well as other lymphoid, myeloid, and dendritic cell markers. Histiocytic sarcoma has strong potential for systemic spread; early diagnosis and treatment are important. Our patient was initially treated with radiation therapy but subsequently developed metastases.

WT1 is not a reliable marker to distinguish reactive from neoplastic astrocyte populations in the central nervous system.

A diagnostic difficulty in neuropathology practice is distinguishing reactive from neoplastic astrocyte populations. This is particularly true in small biopsy samples that lack evidence of increased cellularity or mitotic activity, microvascular proliferation, or necrosis. We performed the current study to validate the previously reported finding that in the central nervous system, the expression of WT1 is limited to neoplastic astrocytes. We retrospectively studied WT1 protein expression by immunohistochemistry (IHC) in 100 formalin-fixed, paraffin-embedded brain tissue samples consisting of 3 normal control tissues, 44 cases of reactive gliosis, 49 gliomas and 4 lesions suspicious for glioma. In normal human cortex, WT1 staining was restricted to vascular endothelium. Most cases of reactive gliosis (82%) showed at least focal WT1 positivity, and analysis of specimens with electrode monitoring lesions showed an inverse relationship between WT1 expression intensity and the number of days from electrode placement to tissue resection. All glioma samples (100%) and all cases suspicious for glioma (100%) showed at least focal WT1 positivity. Our results likely differ from those in the prior report because of differences in tissue fixation and IHC methodology. Thus, our findings indicate that WT1 expression alone is not a reliable feature to distinguish reactive from neoplastic astrocytes.

Intracranial plasmacytoma with apoplectic presentation and spontaneous intracerebral hemorrhage: Case report and review of the literature.

Involvement of the nervous system is not uncommon in patients with multiple myeloma, with polyneuropathy and myelopathy predominating. Intracranial involvement producing neurological symptoms, however, is distinctly uncommon. Massive intraparenchymal hemorrhage from a previously unrecognized intracranial plasmacytoma is exceedingly rare. The authors report the case of a 57-year-old male who presented with sudden onset of severe headache, rapid onset of right-sided weakness and deterioration in level of consciousness while at work. Two years earlier the patient had completed treatment for multiple myeloma and was considered to be in remission, with a recent bone marrow biopsy that was negative, and complete normalization of serum protein electrophoresis. Imaging studies revealed a massive intracerebral hemorrhage with the possibility of an underlying lesion, and the patient was taken for emergent hematoma evacuation and tumor resection. The patient made an excellent recovery and was treated with intracranial radiation. Even in patients with multiple myeloma without evidence of systemic disease following successful treatment, the possibility of unrecognized lesions lingers. The onset of new symptoms referable to potential intracranial pathology in this setting should prompt consideration of intracranial plasmacytoma in the differential diagnosis.

Dephosphorylation of beta-arrestin 1 in glioblastomas.

Beta-Arrestins act as signal terminators for G protein-coupled receptors; they have also been implicated as scaffolding proteins for Src and mitogen-activated protein kinase signaling pathways and transactivators of receptor tyrosine kinases, suggesting their possible role in development and oncogenic signaling. Dephosphorylation of serine 412 is necessary for Src and mitogen-activated protein kinase transactivation. We hypothesized that altered beta-arrestin 1 phosphorylation and activation status could play a role in gliomagenesis. Using monoclonal anti-phospho-(serine 412)- and total beta-arrestin 1 antibodies, we performed immunohistochemistry on 126 human glioma samples and 7 nonneoplastic controls and Western blot analysis on 5 glioblastomas and 5 nonneoplastic controls. We found high constitutive beta-arrestin 1 phosphorylation in nonneoplastic brain tissue, particularly in neurons and neuropil. Most Grade II and III gliomas retained high beta-arrestin 1 phosphorylation. By contrast, most of the glioblastoma samples (58/81) showed nearly complete beta-arrestin 1 dephosphorylation by immunohistochemistry and decreased relative phosphorylation by Western blot. Expression of constitutively activated epidermal growth factor receptor vIII in U251 cells caused decreased beta-arrestin 1 phosphorylation without altering total beta-arrestin 1 levels. These results suggest that beta-arrestin 1 dephosphorylation/inactivation is associated with aspects of the malignant behavior of glioblastomas.

Immunohistochemical assessment of protein phosphorylation state: the dream and the reality.

The development of phosphorylation state-specific antibodies (PSSAs) in the 1980s, and their subsequent proliferation promised to enable in situ analysis of the activation states of complex intracellular signaling networks. The extent to which this promise has been fulfilled is the topic of this review. I review some applications of PSSAs primarily in the assessment of solid tumor signaling pathway activation status. PSSAs have received considerable attention for their potential to reveal cell type-specific activation status, provide added prognostic information, aid in the prediction of response to therapy, and most recently, demonstrate the efficacy of kinase-targeted chemotherapies. However, despite some successes, many studies have failed to demonstrate added value of PSSAs over general antibody immunohistochemistry. Moreover, there is still a large degree of uncertainty about the interpretation of complex and heterogeneous staining patterns in tissue samples and their relationship to the actual phosphorylation states in vivo. The next phase of translational research in applications of PSSAs will entail the hard work of antibody validation, gathering of detailed information about epitope-specific lability, and implementation of methods for standardization.

Granular cell tumor of the neurohypophysis: report of a case with intraoperative cytologic diagnosis.

Cytological techniques including touch and smear preparations are very useful diagnostic modality in the evaluation of central nervous system (CNS) lesions and, in many instances, may be effectively used as the sole modality of tissue preparation for intraoperative consultation. Cytologic preparations offer many advantages over frozen sections for CNS specimens. These include selective examination of multiple areas from small biopsy specimens, superior preservation and details of cellular morphology, fewer artifacts, faster results, and improved cost-effectiveness. We describe the cytologic diagnosis of a granular cell tumor (GCT) of the neurohypophysis in a 33-year-old male who presented with headache and blurred vision. CT scan revealed an enlarged sella with a 2.15 x 2.0 cm pituitary lesion. Transsphenoidal resection of the mass was performed and submitted for intraoperative consultation. Smears and touch preparations were made on a portion of the mass that showed uniform polygonal cells with round to ovoid nuclei and abundant eosinophilic granular cytoplasm. An intraoperative cytological diagnosis of "favor GCT" was rendered. The histologic sections of the remaining material confirmed the diagnosis. Although GCT of the neurohypophysis is very rare, a specific intraoperative cytological diagnosis is possible. We report the clinical, cytological, and pathological findings of a GCT affecting the neurohypophysis.

A pharmacological activator of AMP-activated protein kinase (AMPK) induces astrocyte stellation.

AMP-activated protein kinase (AMPK) represents a key energy-sensing molecule in many cell types. Because astrocytes are key mediators of metabolic signaling in the brain, we have initiated studies on the expression and activation of AMPK in these cells. Treatment of cultured rat cortical astrocytes with a pharmacological AMPK activator, AICA-riboside (AICAR) resulted in a time- and concentration-dependent increase in phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a direct substrate. AICAR treatment also induced a transition from epithelioid to stellate morphology in a time- and concentration-dependent manner. As stellation is indicative of actin cytoskeletal reorganization, the formation of stress fibers and focal adhesions in response to AICAR was assessed. AICAR-induced stellation correlated with F-actin disassembly and focal adhesion dispersal. Furthermore, transient transfection of an activated RhoA construct prevented AICAR-induced stellation, indicating a mechanism upstream of RhoA. Use of pharmacological inhibitor compound C prevented AICAR-induced stellation demonstrating necessity of AMPK activity for the response. Our findings suggest that AMPK mediates morphological alterations of astrocytes in response to energy depletion.

Primary disseminated leptomeningeal oligodendroglioma with 1p deletion. Case report.

The authors report the case of a 2-year-old boy with a primary, diffuse leptomeningeal oligodendroglioma in which the deletion of chromosome arm lp was identified by performing a fluorescence in situ hybridization (FISH) analysis. This previously healthy child initially presented with malaise, anorexia, nausea, vomiting, and macrocephaly. Imaging studies confirmed the presence of hydrocephalus, and a ventriculoperitoneal shunt was placed. The postoperative course was complicated by emesis, continued weight loss, and numerous seizurelike episodes. A contrast-enhanced magnetic resonance imaging study performed approximately 10 weeks postoperatively showed diffuse leptomeningeal thickening and enhancement without evidence of an intraparenchymal mass lesion. A right frontal lobe brain biopsy revealed a hypercellular proliferation of small oligodendroglioma-like cells, which occupied the leptomeninges diffusely and spared the underlying cortical gray matter. The tumor cells displayed prominent perinuclear clearing and had evenly spaced, uniformly round nuclei. Occasional mitotic figures were observed. Background vessels were thin and delicate, and there was no evidence of necrosis. The tumor cells showed strong immunoreactivity for S100 protein; the results of immunohistochemical staining were negative for glial fibrillary acidic protein, vimentin, epithelial membrane antigen, NeuN, and synaptophysin. The deletion of lp was demonstrated by FISH analysis; lq, 19p, and 19q were intact. This appears to be the first reported case of a primary diffuse leptomeningeal oligodendroglioma in which a lp deletion was identified.

Follicular lymphoma of the dura: case report.

OBJECTIVE: We present an unusual dural-based follicular lymphoma with radiological and macroscopic features similar to a meningioma. The unusual location of this tumor and its distinction from meningioma, mucosa-associated lymphoid tissue-type marginal zone B-cell lymphoma of the dura, and intraparenchymal central nervous system lymphoma, dramatically alters the patient's postoperative treatment. The case illustrates the clinical, radiological, and histological relevance of this rare entity. CLINICAL PRESENTATION: A 41-year-old Caucasian man with chronic bifrontal headaches and a raised area over his left frontal cranium that persisted for 1 year presented to the emergency room with nausea and vomiting. His family reported that the patient demonstrated increased irritability and aggressive behavior. A computed tomographic scan revealed a large mass of the left frontal convexity with edema and mass effect. Magnetic resonance imaging scans showed a 5-cm homogeneously enhancing mass in the left posterior frontal lobe. INTERVENTION: Preoperatively, the patient underwent angiography and embolization of the tumor. The patient underwent gross total resection of tumor. The dural-based tumor invaded the cranium and scalp. Neuropathological findings were consistent with low-grade follicular lymphoma. The patient is currently undergoing radiation and chemotherapy. CONCLUSION: The current case represents the first report of extensive intracranial dural involvement by a follicular lymphoma that shows a classic immunophenotype by immunohistochemistry and flow cytometry. The case illustrates the clinical and radiographic similarities between dural-based lymphoma and meningioma. Distinguishing dural-based follicular lymphoma from mucosa-associated lymphoid tissue-type lymphoma and from intraparenchymal primary central nervous system lymphomas, which are more often large cell lymphomas with more aggressive biological behavior, is essential for proper clinical management.