Diffuse Leptomeningeal Spread Research Articles

"Recurrent Pleomorphic Xanthoastrocytoma Presenting with Diffuse Leptomeningeal Spread".

We have read with great interest the recent paper by Grigsby-Rocca et al regarding recurrent pleomorphic xanthoastrocytoma (PXA) with leptomeningeal dissemination. While acknowledging the challenges in managing such cases, we wish to highlight the role of radiotherapy for symptom palliation and potential life extension. We report a case of a 27-year-old woman with recurrent anaplastic PXA and diffuse leptomeningeal spread, who was offered radiotherapy to the spinal axis. Initially presenting with headaches and seizures, she underwent surgical excision, postoperative radiotherapy, and temozolomide. Despite initial disease control, subsequent recurrences required additional surgeries and systemic therapies. With disease progression to leptomeningeal spread, radiotherapy was administered, resulting in clinical stability. This case underscores the importance of considering palliative radiotherapy to improve quality of life and potentially prolong survival in patients with recurrent PXA and leptomeningeal dissemination.

Perineural spread of peripheral neurolymphomatosis to the cauda equina.

Neurolymphomatosis (NL) is a rare manifestation of lymphoma confined to the peripheral nervous system that is poorly understood. It can be found in the cauda equina, but extraspinal disease can be underappreciated. The authors describe how extraspinal NL progresses to the cauda equina by perineural spread and the implications of this on timely and safe diagnostic options. The authors used the Mayo Clinic medical records database to find cases of cauda equina NL with sufficient imaging to characterize the lumbosacral plexus diagnosed from tissue biopsy. Demographics (sex, age), clinical data (initial symptoms, cerebrospinal fluid, evidence of CNS involvement, biopsy location, primary or secondary disease), and imaging findings were reviewed. Ten patients met inclusion and exclusion criteria, and only 2 of 10 patients presented with cauda equina symptoms at the time of biopsy, with 1 patient undergoing a cauda equina biopsy. Eight patients were diagnosed with diffuse large B-cell lymphoma, 1 with low-grade B-cell lymphoma, and 1 with mantle cell lymphoma. Isolated spinal nerve involvement was identified in 5 of 10 cases, providing compelling evidence regarding the pathophysiology of NL. The conus medullaris was not radiologically involved in any case. Lumbosacral plexus MRI was able to identify extraspinal disease and offered diagnostically useful biopsy targets. FDG PET/CT was relatively insensitive for detecting disease in the cauda equina but was helpful in identifying extraspinal NL. The authors propose that perineural spread of extraspinal NL to infiltrate the cauda equina occurs in two phases. 1) There is proximal and distal spread along a peripheral nerve, with eventual spread to anatomically connected nerves via junction and branch points. 2) The tumor cells enter the spinal canal through corresponding neural foramina and propagate along the spinal nerves composing the cauda equina. To diffusely infiltrate the cauda equina, a third phase occurs in which tumor cells can spread circumdurally to the opposite side of the spinal canal and enter contralateral nerve roots extending proximally and distally. This spread of disease can lead to diffuse bilateral spinal nerve disease without diffuse leptomeningeal spread. Recognition of this phasic mechanism can lead to identification of safer extraspinal biopsy targets that could allow for greater functional recovery after appropriate treatment.

Atypical central neurocytoma with leptomeningeal dissemination: a case report

BackgroundCentral neurocytomas represent 0.25–0.5% of all intracranial tumors in adults. Leptomeningeal spread is uncommon, and the exact incidence of meningeal spread is unknown due to sparse literature. We present the clinical course and management outcome of a case of atypical central neurocytoma with leptomeningeal spread.Case presentationA young gentleman, who initially presented with memory loss, was found to have a right intra-axial periventricular mass on imaging. He underwent subtotal resection, and operative histopathology suggested a periventricular atypical neurocytoma. In view of subtotal resection, adjuvant focal radiation therapy was recommended, but he developed headache and blurring of vision 10 days postoperatively. Contrast enhanced craniospinal magnetic resonance imaging (MRI) showed residual primary tumor as well as diffuse leptomeningeal spread. Cerebrospinal fluid cytology also showed malignant cells. After tumor board discussion, craniospinal axis irradiation was advised and delivered. He remained disease-free for 10 months after radiation therapy, but then developed local and spinal recurrence, and offered salvage chemotherapy. His general condition deteriorated following chemotherapy with disease progression, and he was subsequently advised best supportive care.ConclusionLeptomeningeal dissemination in atypical neurocytomas portends an aggressive course and adverse prognosis; management decisions may need tailoring as per individual presentation.

MYCN amplification drives an aggressive form of spinal ependymoma

Spinal ependymal tumors form a histologically and molecularly heterogeneous group of tumors with generally good prognosis. However, their treatment can be challenging if infiltration of the spinal cord or dissemination throughout the central nervous system (CNS) occurs and, in these cases, clinical outcome remains poor. Here, we describe a new and relatively rare subgroup of spinal ependymal tumors identified using DNA methylation profiling that is distinct from other molecular subgroups of ependymoma. Copy number variation plots derived from DNA methylation arrays showed MYCN amplification as a characteristic genetic alteration in all cases of our cohort (n = 13), which was subsequently validated using fluorescence in situ hybridization. The histological diagnosis was anaplastic ependymoma (WHO Grade III) in ten cases and classic ependymoma (WHO Grade II) in three cases. Histological re-evaluation in five primary tumors and seven relapses showed characteristic histological features of ependymoma, namely pseudorosettes, GFAP- and EMA positivity. Electron microscopy revealed cilia, complex intercellular junctions and intermediate filaments in a representative sample. Taking these findings into account, we suggest to designate this molecular subgroup spinal ependymoma with MYCN amplification, SP-EPN-MYCN. SP-EPN-MYCN tumors showed distinct growth patterns with intradural, extramedullary localization mostly within the thoracic and cervical spine, diffuse leptomeningeal spread throughout the whole CNS and infiltrative invasion of the spinal cord. Dissemination was observed in 100% of cases. Despite high-intensity treatment, SP-EPN-MYCN showed significantly worse median progression free survival (PFS) (17 months) and median overall survival (OS) (87 months) than all other previously described molecular spinal ependymoma subgroups. OS and PFS were similar to supratentorial ependymoma with RELA-fusion (ST-EPN-RELA) and posterior fossa ependymoma A (PF-EPN-A), further highlighting the aggressiveness of this distinct new subgroup. We, therefore, propose to establish SP-EPN-MYCN as a new molecular subgroup in ependymoma and advocate for testing newly diagnosed spinal ependymal tumors for MYCN amplification.

Biopsying a spinal cord lesion: A diagnostic dilemma. Case report and review of literature

Spinal cord biopsy is a difficult procedure fraught with the risk of false-negative results or even misdiagnosis in up to 30% of cases. Differential diagnoses of spinal cord lesions include a wide range of inflammatory, infectious and neoplastic diseases. Given the importance of correctly managing these pathologies, it is crucial to avoid delays in making the correct diagnosis in order to improve the patient's outcome. We present here the case of a 21-year-old male with rapidly progressing sphincter and lower limb motor dysfunctions up to complete paraplegia with evidence of thoracic spinal cord lesion on magnetic resonance imaging. None of the blood and cerebrospinal fluid tests pointed to a diagnosis, while a first spinal cord biopsy revealed an inflammatory necrotic process. After several weeks of empirical treatments and clinical stability, the patient started having focal structural seizures that became generalized with local progression of the lesion and diffuse leptomeningeal spread on magnetic resonance imaging. A second spinal cord biopsy found a grade IV glioblastoma with H3 K27M histone mutation. Unfortunately the patient passed away before any treatment could be initiated. In this report, the authors analyze the difficulty of making the rapid, correct diagnosis of a highly malignant intrinsic spinal cord lesion, discussing also possible strategies to avoid diagnostic delays and to improve the outcome of these difficult patients.

ATPS-23MULTIMODALITY TREATMENT FOR METASTATIC, RECURRENT PINEAL PARENCHYMAL TUMOR OF INTERMEDIATE DIFFERENTIATION: A NOVEL TREATMENT APPROACH

INTRODUCTION: Pineal parenchymal tumors of intermediate differentiation (PPTID) represent less than 0.04% of brain tumors. Due to the rarity of this disease, there is no consensus as to appropriate treatment of this tumor. We present a patient with PPTID and our novel approach thereafter. CASE: A 34 year-old male presented with headache, nausea and vomiting, and an MRI showing a 2-cm pineal mass. Biopsy showed PPTID. He underwent whole brain radiation therapy and chemotherapy with carboplatin, bleomycin and VP-16. He showed recurrence after 5-years, after which partial tumor resection was performed and he underwent further treatment with cisplatin/melphalan and radiation. Two years later, MRI showed hydrocephalus and diffuse leptomeningeal spread with several solid tumors, which was treated with a VP shunt. After in-vitro chemosensitivity analysis, the patient was started on temozolamide. He had resolution of symptoms and radiographic masses. Eight months later, patient presented with further symptoms and thrombocytopenia. MRI showed tumor progression and cerebellar hemorrhage. The family elected not to treat and care was withdrawn. METHODS/RESULT: Tumor cells collected from CSF were grown in culture and sensitivity to chemotherapeutic agents was determined. In-vitro chemosensitivity trials showed DM-CHOC-PEN, a novel agent that is currently in phase-2 clinical trials at our institution, and temozolamide each had excellent response with 75% tumor cell death. We elected to treat the patient with temozolamide. CONCLUSION: We took a practical and rational approach of applying several low morbidity treatments to treat this patient's disease. Based off of our chemosensitivity trials, we found excellent results with DM-CHOC-PEN as well as temozolamide. We elected to treat the patient with temozolamide. With this approach, we were able to control this patient's disease for up to 8-years. In cases of rare tumors, we suggest the use of similar rational approaches to individual patients until proven treatment regimens are available.

Clinico‐pathological description of three paediatric medulloblastoma cases with MLL2/3 gene mutations

Clinico‐pathological description of three paediatric medulloblastoma cases with <scp><i>MLL2/3</i></scp> gene mutations

Primary Intraventricular Lymphoma with Diffuse Leptomeningeal Spread at Presentation

Primary Intraventricular Lymphoma with Diffuse Leptomeningeal Spread at Presentation

Middle ear rhabdomyosarcoma infiltrating the petrous with diffuse leptomeningeal spread in a child

We present a case of middle ear rhabdomyosarcoma with intracranial erosion and later presented with diffuse leptomeningeal spread. Such lesions are difficult to eradicate and have a poor prognosis

Preoperative diffuse leptomeningeal spread in a medulloblastoma: Paraplegia following surgery for posterior fossa and call for newer management protocols

Management of patients with medulloblastoma presenting with multiple metastasis in subarachnoid space preoperatively is unclear. An 11–year-old boy presented with vermian medulloblastoma with an unusually long segment cervico-dorsal lesion and suprasellar lesion. The child underwent a posterior fossa craniotomy (prone position) and excision of vermian mass. He developed paraplegia in the immediate postoperative period, the possible causes for which are being discussed. Besides, treatment options for patients presenting with disseminated disease preoperatively have been highlighted. Preoperative chemotherapy to downstage such lesions may be tried and such complications could be avoided.

Boost radiosurgery as a strategy after failure of initial management of pediatric primitive neuroectodermal tumors

The aim in this study was to determine the outcomes of boost stereotactic radiosurgery, specifically Gamma Knife surgery (GKS), for recurrent primitive neuroectodermal tumors (PNETs) in children in whom initial multimodality management had failed. The authors performed a retrospective analysis of 7 patients who underwent a total of 15 GKS procedures for locally recurrent or metastatic PNETs. Nine procedures were directed at the primary site, whereas 6 were directed at distant brain sites. All patients received multimodality therapy, including resection, fractionated radiotherapy, and chemotherapy. The mean interval from diagnosis to first stereotactic radiosurgery was 25.8 months (range 11-35 months). The mean tumor volume was 3.9 cm(3) (range 1.1-13.1 cm(3)), and an average marginal dose of 14.5 Gy (range 9-20 Gy) was administered. Following salvage GKS, 2 patients had early disease progression (median survival of 5 months after GKS). Five patients had late disease progression (complete response in 3, partial response in 1, and stable disease in 1) and a median survival of 30 months after GKS. Four of the 5 patients who had late progression underwent repeat GKS for marginal recurrence. No adverse radiation effects were observed in these 7 patients. The GKS modality was a well-tolerated and useful boost strategy in pediatric patients with PNET and a poor prognosis in whom initial multimodality management had failed. However, local or distant disease progression or diffuse leptomeningeal spread ultimately proved fatal to these patients.

Low‐grade follicular lymphoma in the dura: Rare mimic of meningioma

Lymphomas rarely present as a localized mass within the dura. We report a case of a 72-year-old woman, normally fit and well, who presented with a sudden episode of grand mal seizure. Imaging studies showed an extra-axial mass arising from the dura, with radiologic features characteristic of a meningioma. The mass was surgically excised, and the histologic features were of a grade 1 follicular lymphoma. Analysis using fluorescent in situ hybridization (FISH) demonstrated t(14:18) translocation. A bone marrow aspirate showed focal infiltration of lumbar vertebra by low-grade follicular lymphoma. Intracranial meningeal involvement by non-Hodgkin lymphoma usually occurs in the form of diffuse leptomeningeal spread. It is seen in high-grade lymphomas, often in association with widespread systemic disease. The majority of cases of dural lymphomas reported in the literature have been primary mucosa-associated lymphoid tissue (MALT)-type lymphomas. Most of these presented as localized dural masses mimicking meningiomas. Low-grade follicular lymphoma, either primary or secondarily involving the dura, appears to be an exceedingly rare occurrence.

Clinicopathologic study of pleomorphic xanthoastrocytoma of brain

To study the clinicopathologic features, treatment response and prognosis of pleomorphic xanthoastrocytoma (PXA). Amongst a total of 6 287 patients with central nervous system tumors encountered in Nanjing General Hospital of PLA during the period from 1980 to 2004, 15 cases of PXA were found. Two additional cases of PXA were also retrieved from the authors' consultation files. The clinicopathologic features of the 17 cases were studied. Follow-up information was available in 10 patients. The age of the patients ranged from 12 to 55 years (mean = 30.8 years). The male-to-female ratio was 6:11. Commonest clinical symptoms included seizures, headaches and dizziness. The tumors in 16 patients were located in the superficial cerebral cortex (94.1%). Seven cases (41.2%) involved the temporal lobe. The size of the tumors varied from 2 to 7 cm (mean = 4.3 cm). Cystic degeneration was noted in 9 cases. For those in-house cases, total tumor excision was performed in 12 patients and subtotal tumor excision was performed in 3 patients. Amongst the 10 patients with follow-up information available, 8 were alive. The post-operative survival ranged from 10 months to more than 13 years (mean survival = 6 years). Classic histopathologic features included an admixture of mononuclear cells, bizarre multinucleated giant cells, spindled cells and lipid-rich vacuolated cells. The tumor cells were associated with abundant lymphocytes and reticulin fibers. They showed little tumor necrosis or mitotic activity. Immunohistochemical study demonstrated diffuse positive staining for glial fibrillary acidic protein, vimentin and S-100 protein. Seventy-seven percent of the cases also showed positive staining for CD34. One case had anaplastic transformation, with increased mitotic activity (mitotic count >or= 5 per 10 high power fields). The tumor cells infiltrated the underlying cerebral cortex with extension into perivascular spaces in 2 cases. Radiologic examination revealed tumor recurrence with diffuse leptomeningeal spread in 1 case. PXA is low-grade glial tumor, corresponding to WHO grade II. Cases with typical pathologic features and total tumor excision carry favorable prognosis. Local recurrence or anaplastic transformation may occur in rare examples. Histologically, PXA can be mistaken as WHO grade IV giant cell glioblastoma, as both entities possess tumor giant cells. PXA however harbors lipiodized astrocytes and lacks coagulative tumor necrosis and high mitotic activity. Frequent expression of CD34 in PXA is also helpful in differential diagnosis.

Concurrent chemotherapy and reduced-dose cranial spinal irradiation followed by conformal posterior fossa tumor bed boost for average-risk medulloblastoma: efficacy and patterns of failure

Purpose To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated with concurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost. Methods and materials Thirty-three patients with average risk (defined as ≤1.5 cm 2 of residual tumor after resection, age >3 years, and no involvement of the cerebrospinal fluid or spine [M0]) medulloblastoma were diagnosed at our institution between January 1994 and December 2001. They were enrolled in an institutional pilot protocol consisting of concurrent chemotherapy (vincristine), reduced-dose cranial spinal irradiation (2340 cGy), a conformal primary tumor bed boost (3240 cGy), followed by eight cycles of chemotherapy (vincristine, cisplatin, and lomustine or cyclophosphamide). The median age at diagnosis of the 33 patients was 7 years (range, 3–21 years). The male/female patient ratio was 2.4:1. The median follow-up of the entire group was 37 months (range, 6–96 months), and the median follow-up of the survivors was 44 months (range, 10–96 months). Results The 5-year estimated disease-free survival rate, as determined by Kaplan-Meier plots, was 86% (±12.6%, 95% confidence interval). The 5-year estimated disease-free posterior fossa control and primary tumor bed control rates were both 94% (±8.2%, 95% confidence interval). The patterns of failure included 2 patients with distant central nervous system failure only, 1 patient who developed local primary tumor bed failure, posterior fossa failure, and diffuse leptomeningeal spread simultaneously, and 1 patient with failure in the high-dose, primary tumor bed field. No patient experienced isolated posterior fossa failure outside the high-dose boost region. Conclusion The treatment of average-risk medulloblastoma with chemotherapy, reduced-dose cranial spinal irradiation, and a conformal tumor bed boost results in survival rates and local control rates comparable to those in contemporary studies. A reduction in the amount of posterior fossa treated to the high dose is possible. These results need to be corroborated in a large, cooperative group study.