T cell deficiency precipitates antibody evasion and emergence of neurovirulent polyomavirus.

JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease in immunocompromised patients. Inherited and acquired T cell deficiencies are associated with PML. The incidence of PML is increasing with the introduction of new immunomodulatory agents, several of which target T cells or B cells. PML patients often carry mutations in the JCPyV VP1 capsid protein, which confer resistance to neutralizing VP1 antibodies (Ab). Polyomaviruses (PyV) are tightly species-specific; the absence of tractable animal models has handicapped understanding PyV pathogenesis. Using mouse polyomavirus (MuPyV), we found that T cell deficiency during persistent infection, in the setting of monospecific VP1 Ab, was required for outgrowth of VP1 Ab-escape viral variants. CD4 T cells were primarily responsible for limiting polyomavirus infection in the kidney, a major reservoir of persistent infection by both JCPyV and MuPyV, and checking emergence of these mutant viruses. T cells also provided a second line of defense by controlling the outgrowth of VP1 mutant viruses that evaded Ab neutralization. A virus with two capsid mutations, one conferring Ab-escape yet impaired infectivity and a second compensatory mutation, yielded a highly neurovirulent variant. These findings link T cell deficiency and evolution of Ab-escape polyomavirus VP1 variants with neuropathogenicity.

Myxopapillary Ependymoma with Anaplastic Features: A Case Series and Review of the Literature.

BACKGROUND: Myxopapillary ependymomas (MPEs) with anaplastic features are rarely reported, with only 21 cases identified to date, and long-term recurrence is rarely presented. A case series is presented to expand understanding of this disease by describing 3 unique cases, including 2 that arose from MPE after a prolonged clinical course. METHODS: A literature review was performed, and 3 cases of MPE with anaplastic features from our institution were included. RESULTS: Patient 1 was a 13-year-old boy who presented with an avidly enhancing intradural lumbar mass. On gross total resection, the tumor was found to be a solid mass with areas of myxopapillary architecture and MIB-1 (Ki-67) index of 12%. Patient 2 was a woman who initially presented at age 22 with a lumbosacral tumor that was treated with surgery and radiation. A recurrent tumor was resected at age 24. At age 50, the patient presented with a large heterogeneous exophytic mass in the sacrum extending into the presacral space and Ki-67 index of 8%. This was treated with complete resection. Patient 3 was a man who initially presented at age 35 with a lower thoracic, upper lumbar mass at L2 extending into the sacrum. Following resection and radiation, a metastatic focus followed an indolent course until causing pain at the age of 48. Ki-67 index was 16%. CONCLUSIONS: The presented cases of MPE with anaplastic features make a total of 24 cases on record in the medical literature and demonstrate 2 examples of late recurrence.

Malignant spindle cell tumors of the posterior fossa in children: case series and review of management.

OBJECTIVE: The WHO Classification of Tumours of the Central Nervous System (2016) classifies nonmeningothelial malignant spindle cell tumors involving the extraaxial tissues of the posterior fossa as melanocytic tumors and malignant mesenchymal tumors (sarcomas). The objective of this study was to conduct a review of the literature pertaining to the management strategies of posterior fossa malignant spindle cell tumors in the pediatric population. METHODS: The authors performed an institutional search of their pathology database for patients younger than 18 years of age who presented with posterior fossa malignant spindle cell tumors. A literature review was also performed using the PubMed database, with "posterior fossa" or "spindle cell tumors" or "Ewing sarcoma" or "high-grade" or "spindle cell sarcoma" or "leptomeningeal melanocytoma" as keywords. The database search was restricted to pediatric patients (age ≤ 18 years). Parameters reported from the literature review included patient age, tumor location, presenting symptoms, treatment modalities (resection, chemotherapy, and/or radiotherapy), leptomeningeal spread at or after the time of treatment, and follow-up length and resulting outcome. RESULTS: The authors report 3 rare cases of posterior fossa malignant spindle cell tumors, including Ewing sarcoma in a 13-year-old male; high-grade spindle cell sarcoma, not otherwise specified in a 10-year-old male; and primary leptomeningeal melanocytoma in a 16-year-old female. All 3 patients underwent resection and radiotherapy and either chemotherapy or targeted immunotherapy. At the last follow-up, all patients were alive with either resolution or stable disease. CONCLUSIONS: A review of these 3 cases and the existing literature support managing patients with intracranial malignant spindle cell tumors with multimodal therapy that can include a combination of resection, radiotherapy, and chemotherapy or immunotherapy to prolong progression-free and overall survival.

Necrotising myopathy and concurrent thyroiditis in a patient with COVID-19 infection.

A 76-year-old man with hypogammaglobulinemia on monthly intravenous immunoglobulin infusions presented to the hospital with fever, cough, and shortness of breath and was diagnosed with COVID-19 pneumonia requiring intensive care unit admission but not intubation. He was treated with convalescent plasma, remdesivir and corticosteroids. Sixteen days into his hospitalisation he began to report weakness without sensory symptoms and was found on biopsy to have a necrotising myopathy.

Neutrophil-induced ferroptosis promotes tumor necrosis in glioblastoma progression.

Tumor necrosis commonly exists and predicts poor prognoses in many cancers. Although it is thought to result from chronic ischemia, the underlying nature and mechanisms driving the involved cell death remain obscure. Here, we show that necrosis in glioblastoma (GBM) involves neutrophil-triggered ferroptosis. In a hyperactivated transcriptional coactivator with PDZ-binding motif-driven GBM mouse model, neutrophils coincide with necrosis temporally and spatially. Neutrophil depletion dampens necrosis. Neutrophils isolated from mouse brain tumors kill cocultured tumor cells. Mechanistically, neutrophils induce iron-dependent accumulation of lipid peroxides within tumor cells by transferring myeloperoxidase-containing granules into tumor cells. Inhibition or depletion of myeloperoxidase suppresses neutrophil-induced tumor cell cytotoxicity. Intratumoral glutathione peroxidase 4 overexpression or acyl-CoA synthetase long chain family member 4 depletion diminishes necrosis and aggressiveness of tumors. Furthermore, analyses of human GBMs support that neutrophils and ferroptosis are associated with necrosis and predict poor survival. Thus, our study identifies ferroptosis as the underlying nature of necrosis in GBMs and reveals a pro-tumorigenic role of ferroptosis. Together, we propose that certain tumor damage(s) occurring during early tumor progression (i.e. ischemia) recruits neutrophils to the site of tissue damage and thereby results in a positive feedback loop, amplifying GBM necrosis development to its fullest extent.

Dilated Epidural Venous Plexus Causing Radiculopathy: A Report of 2 Cases and Review of the Literature.

BACKGROUND: A dilated epidural venous plexus (DEVP) is a rare cause of radiculopathy, back pain, cauda equina syndrome, and other neurological symptoms. This vascular mass can be secondary to inferior vena cava obstruction, portal hypertension, vascular agenesis, and hypercoagulable states. Although rare, DEVP should be considered in the differential diagnosis for patients who present with lumbar radiculopathy. CASE DESCRIPTION: We present 2 cases involving patients with lumbar DEVP as well as a literature review of the role of hypercoagulability, vascular anatomy, and inferior vena cava thrombosis in the development of DEVP. The first patient had a history of recurrent deep vein thrombosis, systemic lupus erythematosus, and antiphospholipid syndrome. The diagnosis of DEVP was determined after intraoperative biopsy. The patient reported symptom resolution at her 6-month postoperative appointment. The second patient developed DEVP associated with Klippel-Trenaunay syndrome. She presented with back pain and leg weakness, and DEVP was diagnosed via magnetic resonance imaging. A neurosurgeon is currently following the patient. We believe this is the first case of Klippel-Trenaunay syndrome associated with DEVP. CONCLUSIONS: If a patient presents with an enhancing epidural lesion on magnetic resonance imaging and neurological symptoms, DEVP should be considered in the differential diagnosis. Additionally, a search for inferior vena cava thrombosis should be performed as well as risk factors for venous hypertension and hypercoagulable states.

Immune mediated necrotizing myopathy: A rare complication of statin therapy.

Immune mediated necrotizing myopathy (IMNM) is part of the inflammatory myopathies group of diseases and presents with muscle weakness, myalgias and elevated serum creatine phosphokinase (CPK). Statin-induced IMNM is a rare complication. We present a patient with IMNM secondary to simvastatin use. The patient presented with proximal myopathy, dysphagia, and elevated creatinine kinase levels, and was subsequently found to have anti-3- hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies with a necrotizing process on muscle biopsy. This patient's case was further complicated by sequelae of multiple disease processes, ultimately leading to deterioration of his health.

Suprasellar central nervous system ganglioneuroblastoma: a case in a 9-year-old child and review of the literature.

PURPOSE: Intracranial ganglioneuroblastomas are incredibly rare neuroectodermal tumors with only 8 described cases total, 5 of those having imaging findings METHODS: Here we present a 9-year-old female patient with 4 months progressive headaches, personality changes, and vomiting. We also present a review of the current literature of intracranial ganglioneuroblastomas. RESULTS: Imaging demonstrated a partially calcified suprasellar mass measuring 4.6 × 6.3 × 5 cm composed of both solid and cystic components, diagnosed to be a ganglioneuroblastoma, with mass effect on the lateral and 3rd ventricles, with a midline shift of right to left of 6-7 mm. She was treated with subtotal surgical resection, an intensive chemotherapeutic regimen, and radiation and has no residual disease on imaging 1 year and 4 months status post-surgery. CONCLUSION: To our knowledge, this is the first case of a ganglioneuroblastoma to mimic a craniopharyngioma based upon imaging findings and suprasellar location. As these cases are extremely rare, an optimal therapeutic regimen has not been defined. However, a combination of surgical resection, chemotherapy, and radiation therapy can be effective, as shown here with successful treatment and no evidence of residual disease.

Dural Extranodal Marginal Zone Lymphoma in an XRCC2 Mutation Carrier.

Dural extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a rare entity without an associated recurrent genetic abnormality. Only one case has been described in a woman with history of breast carcinoma without a known genetic predisposition. Here, we report a case of a 56-year-old woman heterozygous for XRCC2 mutation with a history of Graves' disease and bilateral breast carcinomas, who was found to have a diffusely infiltrative extra-axial mass in the high parietal convexity with infiltration into the adjacent superior sagittal sinus. The morphologic, immunophenotypic, and molecular findings were diagnostic of MALT lymphoma. Staging bone marrow demonstrated involvement by the neoplasm. Although the study was limited to only the clinically significant laboratory evaluation, it may serve as an important addition to the current knowledge of the pathogenic potential of a loss of function mutation in this rarely reported cancer predisposition gene.

Neuroleukemiosis: Diagnosis and management.

An exceedingly rare manifestation of leukemia, termed neuroleukemiosis, involves peripheral nerve infiltration by leukemic cells. Patients with neuroleukemiosis typically present with a peripheral neuropathy and/or chloromatous masses. The diagnosis is supported by, and established with, electrophysiologic testing, imaging, histopathology, and immunophenotyping. We present the case of 21 year old male with multiply relapsed M4 type of acute myelogenous leukemia (AML) who presented with extremity pain and was subsequently found to have multiple cervical, thoracic, and lumbosacral nerve root masses. A diagnosis of neuroleukemiosis was established via CT-guided biopsy and immunophenotyping. The patient's neuroleukemiosis responded well to chemotherapy, donor lymphocyte infusions, and spinal irradiation. The literature is reviewed regarding this interesting and rare clinical condition.

Utility of Early Postoperative Magnetic Resonance Imaging After Glioblastoma Resection: Implications on Patient Survival.

BACKGROUND: The standard of care for glioblastoma is surgical resection followed by combination temozolomide and radiation. Magnetic resonance imaging (MRI) is used preoperatively for tumor resection planning. In some instances, MRI is also obtained postoperatively to assess for any complications and to determine extent of resection. There is some question whether early routine postoperative imaging of patients after tumor resection is beneficial to long-term outcomes, especially with the increased scrutiny of increasing health care costs. METHODS: In this study we retrospectively analyze patients with glioblastoma treated at our institution, comparing the difference in overall survival and treatment regimens between patients who had early postoperative MRI versus patients who did not. RESULTS: We determine that in our cohort of 125 patients, those with early postoperative MRI had no statistically significant overall survival difference compared with patients with no early postoperative MRI (P = 0.996). The median survival for the group with postoperative MRI was 378 days (95% confidence interval [CI], 242-443 days), and the median survival for the group without postoperative MRI was 308 days (95% CI, 203-445 days). Early postoperative MRI also did not significantly alter therapeutic regimens. CONCLUSIONS: Although early postoperative MRI may not significantly affect patient overall survival from a statistical standpoint or therapeutic regimens, this type of imaging may be important to hone resident and attending skill. We encourage other institutions to perform similar analyses to determine the overall survival benefit of early postoperative imaging after glioma resection for patients with glioblastoma.

Crossed Aphasia as a Manifestation of Glioblastoma.

Language and speech function is commonly accepted to be a heavily lateralized function. Greater than 95% of right-handed individuals have left hemispheric dominance for language, and reports in the literature of crossed aphasia (language deficits in a right-handed individual from right-sided pathology) are scant. We report the case of a 52-year-old woman presenting with crossed aphasia from a right temporal glioblastoma. We then expand on a discussion of crossed aphasia in the setting of brain tumors.

The predictive potential of hyponatremia for glioblastoma patient survival.

Glioblastoma is a devastating malignancy with a dismal survival rate. Currently, there are limited prognostic markers of glioblastoma including IDH1, ATRX, MGMT, PTEN, EGFRvIII, and others. Although these biomarkers for tumor prognosis are available, a surgical biopsy must be performed for these analyses, which has morbidity involved. A non-invasive and readily available biomarker is sought after which provides clinicians prognostic information. Sodium is an electrolyte that is easily and quickly obtained through analysis of a patient's serum. Hyponatremia has been shown to have a predictive and negative prognostic indication in multiple cancer types, but the role of glioblastoma patients' serum sodium at the time of diagnosis in predicting glioblastoma patient survival has not been determined. We assessed whether hyponatremia at the time of glioblastoma diagnosis correlates to patient survival and show that in our cohort of 200 glioblastoma patients, sodium, at any level, did not significantly correlate to glioblastoma survival, unlike what is seen in multiple other cancer types. We further demonstrate that inducing hyponatremia in an orthotopic murine model of glioblastoma has no effects on tumor progression and survival.

Double dermal sinus tracts of the cervical and thoracic regions: a case in a 3-year-old child and review of the literature.

INTRODUCTION: Dermal sinus tracts are rare congenital abnormalities characterized by an epithelium-lined tract that extends from the subcutaneous tissue to the underlying thecal sac or neural tube. These developmental anomalies can present asymptomatically with a cutaneous dimple or with devastating complications including recurrent episodes of meningitis, or neurological complications including paralysis. Dermal sinus tracts generally occur as single lesions, and the presentation of midline double dermal sinus tracts of the cervical and thoracic regions has not been previously described. METHODS: Here, we present the case of a 3-year-old girl suffering from recurrent episodes of myelitis, paraparesis, and intramedullary intradural masses, who was diagnosed with double dermal sinus tracts of the cervical and thoracic regions. We also present a summary of all previous reported cases of multiple dermal sinus tracts. RESULTS: Our patient was successfully treated surgically and is now 2 years status post her last procedure with a significant improvement in her neurologic function and normal muscle strength and tone for her age, and there was no recurrence of her symptoms. CONCLUSIONS: Early treatment with prophylactic surgery should be performed when possible, but removal of these lesions once symptoms have arisen can also lead to success, as in the case presented here. Complete excision and intradural exploration is required to excise the complete tract.

Correlation of Histopathology and Clinical Symptoms in Meralgia Paresthetica.

Meralgia paresthetica is a neuropathic pain disorder resulting from an entrapment neuropathy of the lateral femoral cutaneous nerve. This condition results in pain, paresthesias and numbness over the anterolateral aspect of the thigh. We present a case of meralgia paresthetica and discuss both the clinical and histopathological findings as they relate to one another. We report a case of meralgia paresthetica refractory to conservative treatment who underwent neurectomy with successful treatment of symptoms. Histopathological examination revealed moderate loss of myelinated axons with some axonal atrophy. The distinct pathologic findings were axonal regeneration clusters and thinly myelinated axons as well as moderate perineurial thickening. These findings corresponded well to the patient's preoperative symptoms of paresthesias and pain. This case serves to shed light on the pathophysiology of meralgia paresthetica and its clinical presentation. It also shows the role of surgical treatment in cases refractory to conservative management in order to alleviate painful symptoms.

Orbital Epstein-Barr Virus-Positive Polymorphic B-Cell Lymphoproliferative Disorder in an Apparently Immunocompetent Woman.

We report a rare case of Epstein-Barr virus (EBV)-positive polymorphic B-cell lymphoproliferative disorder (LPD) involving the lacrimal gland of a 28-year-old, apparently immunocompetent woman. She presented with a chief complaint of orbital swelling and tenderness and was found to have a lesion involving the right lacrimal gland and distal superior and lateral rectus muscles. Histology of the lesion revealed histiocytes with pleomorphic nuclei, reactive lymphocytes, and scattered cells that resembled the Reed-Sternberg (R-S) cells of classical Hodgkin lymphoma. The R-S-like cells were positive for PAX5 and CD30 and negative for CD15, supporting a diagnosis of polymorphic B-cell LPD. In situ hybridization for EBV-encoded RNA demonstrated the presence of EBV. Most EBV-positive polymorphic B-cell LPDs are associated with immunodeficiency. However, the patient described is HIV-negative and has no identifiable defects in immunoglobulin levels or cell-mediated immunity. This raises the question of whether she has an underlying immunodeficiency resulting from subtle changes in T-cell physiology, or whether chronic EBV infection contributed to her immune dysfunction through an unclear mechanism. The orbital mass partially regressed with chemotherapy, and the patient has done well clinically with no recurrence of this EBV-LPD for over 2 years.

Case Report: A Rosette-forming Glioneuronal Tumor in the Tectal Plate in a Patient with Neurofibromatosis Type I.

We report the case of a 41-year-old female with neurofibromatosis Type 1 (NF1) who developed a rosette-forming glioneuronal tumor (RGNT) in the tectal plate. This tumor was diagnosed in 2002 when the patient presented with obstructive hydrocephalus, which was subsequently treated with a ventriculoperitoneal shunt and then an endoscopic third ventriculostomy. Initially thought to be a pilocytic astrocytoma, it was followed with serial magnetic resonance imaging (MRI) until tumor progression and development of a large fourth ventricular cystic component prompted resection via suboccipital craniotomy. Histological examination demonstrated an RGNT, a WHO Grade 1 tumor, with neurocytic rosettes, perivascular pseudorosettes, and elements resembling a pilocytic astrocytoma. Initially, the patient did well after her craniotomy, but postoperative complications set in that eventually led to her death. In this case report, we describe a relatively rare tumor that, despite its benign nature, leads to frequent complications and deficits due to its surgically challenging location. Along with previously reported examples, this cases raises the possibility of a causal relationship between NF1 and RGNT.

Intraventricular Undifferentiated Pleomorphic Sarcoma: A Case Report.

Undifferentiated pleomorphic sarcoma is a histologic diagnosis based on cell morphology. These tumors are found throughout the body. They are rarely found in the central nervous system and almost never occur as a primary intraventricular tumor. We present the unusual case of a 68-year-old woman with an intraventricular undifferentiated pleomorphic sarcoma. We go on to discuss the clinical presentation, radiographic characteristics, and management paradigm for these rare lesions. Our patient presented with acute confusion, inability to balance a checkbook, and gait imbalance. CT and MRI demonstrated a 4 x 3.6 x 3.6 cm enhancing lesion in the left lateral ventricle abutting the foramen of Monro. Pathology revealed an undifferentiated pleomorphic sarcoma.

Hybrid Neurofibroma-Schwannoma.

Neurofibromas and schwannomas are common lesions that may be idiopathic or may occur in association with neural crest genetic syndromes such as neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. A hybrid tumor that contains pathological characteristics of both neurofibroma and schwannoma has been described as a rare entity. We present the clinical, radiographic, and pathological findings of such a case.

Duplicate filum terminale noted in an adult: a rare finding.

This is the first reported case of an adult presenting with tethering symptoms, limb discrepancy on physical examination, a low-lying spinal cord, and duplicate filum terminale discovered intraoperatively. Intraoperative imaging and pathological analysis of a specimen confirmed the diagnosis of duplicate filum. This is the first reported adult case with duplication of the filum terminale. Release of both fila was necessary in this case to relieve the tethering symptoms.