Isolated Lymphomatoid Granulomatosis of the Central Nervous System Mimicking Trigeminal Neuropathy, Bell's Palsy, and Glioblastoma in an Epstein-Barr-Negative Immunocompetent Host: A Case Report.

Lymphomatoid granulomatosis is an Epstein-Barr virus-associated lymphoproliferative B-cell neoplasm that typically involves multiple organ systems. This disease is exceedingly rare when confined to the central nervous system (CNS), usually presenting as a mass lesion or diffuse disease, with no existing standard of care. We present the case of a 67-year-old patient who had a unique and insidious course of isolated CNS lymphomatoid granulomatosis. The disease first presented with cranial neuropathies involving the trigeminal and facial nerves that were responsive to steroids both clinically and radiographically. Two years later, the disease manifested as a parietal mass mimicking high-grade glioma that caused homonymous hemianopsia. The patient underwent craniotomy for resection and was treated with rituximab after surgery. The patient has achieved progression-free survival more than three years after the surgery. Surgical debulking and post-procedural rituximab resulted in favorable survival in a case of isolated CNS lymphomatoid granulomatosis. An intracranial mass preceded by steroid-responsive cranial neuropathies should raise suspicion for lymphoproliferative disorder.

Perinatal hypoxic-ischemic brain injury: What's behind the "ribbon effect"?

Ribbon effect describes a perceived macroscopic color reversal of the gray and white matter, characterized by a pale cortex and diffusely dusky underlying white matter. This finding is thought to be unique to the perinatal period and indicative of hypoxic-ischemic injury. However, the clinical and microscopic correlates of this macroscopic finding have not been clearly defined. A 21-year retrospective study of autopsies was performed. Ribbon effect was seen in 190 subjects, ages 20 weeks gestation to 9.5 months adjusted age. Clinical associations and radiographic findings were similar in ribbon effect cases and controls. A variety of histologic findings were observed including acute neuronal injury, diffuse white matter gliosis, and white matter necrosis. Only white matter vascular congestion was significantly correlated to the macroscopic severity of ribbon effect; the severity of white matter injury and acute neuronal injury were not significantly correlated to ribbon effect. While hypoxic-ischemic changes were present in nearly all cases of ribbon effect, the location, severity, and chronicity of these changes varied considerably, and similar findings were observed in controls. The presence of ribbon effect therefore does not predict microscopic findings apart from vascular congestion, highlighting the importance of microscopic examination in perinatal brain autopsies.

Clinical Evaluation of IDH Mutation Status in Formalin-Fixed Paraffin-Embedded Tissue in Gliomas.

BACKGROUND AND OBJECTIVE: Determination of isocitrate dehydrogenase (IDH) 1/2 mutational status is crucial for a glioma diagnosis. It is common for IDH mutational status to be determined via a two-step algorithm that utilizes immunohistochemistry studies for IDH1 R132H, the most frequent variant, followed by next-generation sequencing studies for immunohistochemistry-negative or immunohistochemistry-equivocal cases. The objective of this study was to evaluate adding a rapid real-time polymerase chain reaction (RT-PCR) assay to the testing algorithm.  METHODS: We validated a modified, commercial, qualitative, RT-PCR assay with the ability to detect 14 variants in IDH1/2 in formalin-fixed paraffin-embedded glioma tumor specimens. The assay was validated using 51 tumor formalin-fixed paraffin-embedded specimens. During clinical implementation of this assay, 48 brain tumor specimens were assessed for IDH result concordance and turnaround time to result. RESULTS: Concordance between the RT-PCR and sequencing and IHC studies was 100%. This RT-PCR assay also showed concordant results with IHC for IDH1 R132H for 11 of the 12 (92%) tumor specimens with IDH mutations. The RT-PCR assay yielded faster results (average 2.6 days turnaround time) in comparison to sequencing studies (17.9 days), with complete concordance. CONCLUSIONS: In summary, we report that this RT-PCR assay can reliably be performed on formalin-fixed paraffin-embedded specimens and has a faster turnaround time than sequencing assays and can be clinically implemented for determination of IDH mutation status for patients with glioma.

Case Report: Multilevel Ossification of the Ligamentum Flavum in a Patient With Spinal Osteoblastoma.

Introduction: Spinal osteoblastomas are primary benign bone tumors most commonly presenting as diffuse back pain in young adults. Rarely, spinal osteoblastoma is associated with ossification of the ligamentum flavum (OLF), a form of ectopic bone formation, which can present with myelopathy. This report highlights a unique case of a patient with spinal osteoblastoma, associated OLF, and thoracic myelopathy. Case Description: The patient presented with subtle myelopathy consisting of mid-thoracic back pain, paresthesias, and gait instability. Imaging findings were suggestive of spinal osteoblastoma with multifocal OLF. The patient was consented for thoracic decompression and stabilization at the T6-10 levels. Histopathology confirmed osteoblastoma with associated OLF. At follow up, the patient's neurological symptoms had completely resolved. Conclusion: This case describes management for a rare presentation of osteoblastoma with associated OLF and myelopathy. Surgeons should be wary of disproportionate neurological compromise when spinal osteoblastoma is associated with OLF. Further study is required to elucidate the pathogenesis of this condition.

Histopathologic quantification of viable tumor versus treatment effect in surgically resected recurrent glioblastoma.

PURPOSE: The prognostic impact of the histopathologic features of recurrent glioblastoma surgical specimens is unknown. We sought to determine whether key histopathologic characteristics in glioblastoma tumors resected after chemoradiotherapy are associated with overall survival (OS). METHODS: The following characteristics were quantified in recurrent glioblastoma specimens at our institution: extent of viable tumor (accounting for % of specimen comprised of tumor and tumor cellularity), mitoses per 10 high-power fields (0, 1-10, > 10), Ki-67 proliferative index (0-100%), hyalinization (0-6; none to extensive), rarefaction (0-6), hemosiderin (0-6), and % of specimen comprised of geographic necrosis (0-100%; converted to 0-6 scale). Variables associated with OS in univariate analysis, as well as age, eastern cooperative oncology group performance status (ECOG PS), extent of repeat resection, time from initial diagnosis to repeat surgery, and O6-methylguanine-DNA methyltransferase promoter methylation, were included in a multivariable Cox proportional hazards model. RESULTS: 37 specimens were assessed. In a multivariate model, high Ki-67 proliferative index was the only histopathologic characteristic associated with worse OS following repeat surgery for glioblastoma (hazard ratio (HR) 1.3, 95% CI 1.1-1.5, p = 0.003). Shorter time interval from initial diagnosis to repeat surgery (HR 1.11, 95% CI 1.02-1.21, p = 0.016) and ECOG PS ≥ 2 (HR 4.19, 95% CI 1.72-10.21, p = 0.002) were also independently associated with inferior OS. CONCLUSION: In patients with glioblastoma undergoing repeat resection following chemoradiotherapy, high Ki-67 index in the recurrent specimen, short time to recurrence, and poor PS are independently associated with worse OS. Histopathologic quantification of viable tumor versus therapy-related changes has limited prognostic influence.