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.

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.

Looks like a stroke, acts like a stroke, but it's more than a stroke: a case of cerebral mucormycosis.

Mucormycosis is a fungus that exhibits angiocentric growth and can cause a thrombotic arteritis. Infection with this organism is uncommon and cerebral involvement is most often secondary to direct invasion through the paranasal sinuses. Here, we present a case of mucormycosis with cerebral involvement without sinus disease, which resulted in ischemic stroke with rapid progression resulting in death.

Giant cell angiofibroma or localized periorbital lymphedema?

Giant cell angiofibroma represents a rare soft tissue neoplasm with a predilection for the orbit. We recently encountered a mass removed from the lower eyelid of a 56-year-old female that histopathologically resembled giant cell angiofibroma. The process consisted of haphazardly arranged CD34-positive spindled and multinucleated cells within an edematous, densely vascular stroma. However, the patient had recently undergone laryngectomy and radiotherapy for a laryngeal squamous cell carcinoma. A similar mass had arisen on the contralateral eyelid, and both had developed several months post-therapy. Lymphedema of the orbit can present as tumor-like nodules and in some cases may share histopathologic features purported to be characteristic of giant cell angiofibroma. A relationship between giant cell angiofibroma and lymphedema has not been established, but our case suggests there may be one. The potential overlap of these two conditions should be recognized, as should other entities that may enter the differential diagnosis.

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.

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.

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.

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.

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.

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.

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.

From the Archives of the AFIP. Pediatric orbit tumors and tumorlike lesions: osseous lesions of the orbit.

Many extraocular masses involving the pediatric orbit have an osseous origin. The most common is the dermoid inclusion cyst; these cystic lesions may contain lipid and are most often found near the zygomaticofrontal suture, adjacent to an indolent-appearing erosion of bone. Some primary bone lesions may involve the orbit, producing a lytic or dense lesion with enlargement of the bone; these lesions include fibrous dysplasia, juvenile ossifying fibroma, and osteosarcoma. Fibrous dysplasia tends to produce a mass of ground-glass appearance with longitudinal osseous expansion, whereas juvenile ossifying fibroma is likely to produce a mixed lytic and sclerotic lesion and focal osseous enlargement. Osteosarcoma causes marked bone destruction and variable osteoid production. Langerhans cell histiocytosis, an idiopathic reticuloendothelial proliferative disorder, tends to involve the bones of the skull, especially the lateral orbital roof; it produces lytic destruction of bone with a sclerotic rim and a large intraorbital soft-tissue mass. Granulocytic sarcoma is a solid tumor that may occur in children with myelogenous leukemia. These tumors tend to arise in the subperiosteum of the lateral orbital wall, although they usually do not disrupt the bone. Finally, the orbit is a common site for bone metastases from neuroblastoma, which cause aggressive periosteal reaction in the orbital roof or lateral wall. The last three conditions are often bilateral. At imaging evaluation, osseous lesions may appear similar to each other and to nonosseous masses of the orbit. Knowledge of the pathologic features of these tumors and how these features are reflected in their imaging appearances may help radiologists differentiate them.

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.

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.

From the archives of the AFIP: Pediatric orbit tumors and tumorlike lesions: neuroepithelial lesions of the ocular globe and optic nerve.

Tumors and tumorlike lesions of the globe and optic nerve in children represent a different histologic spectrum than in adults; the imaging appearances of these lesions reflect their pathologic features. Retinoblastoma is a tumor of infancy and the most common intraocular tumor in children. There are heritable and nonheritable forms. The most common clinical finding is leukocoria. The differential diagnoses of this sign include several nonneoplastic lesions: Persistent hyperplastic primary vitreous is a congenital persistence of an embryonic structure causing a retrolental mass. The primitive vasculature may produce a septum in the posterior chamber. Coats disease is a vascular malformation of the retina that produces a lipoproteinaceous subretinal exudate. The vascular malformation enhances with intravenous contrast material, and the fat-containing subretinal exudate does not. Larval endophthalmitis is a granulomatous reaction to the dead or dying larvae of Toxocara canis or T. cati. The most important feature that allows differentiation of retinoblastoma from these so-called pseudoretinoblastomas is the presence of calcification in the former. Medulloepithelioma has two histologic forms; the teratoid type may contain calcifications, but it usually arises anteriorly from the ciliary body rather than posteriorly from the retina. Optic nerve glioma is the most common tumor of the optic nerve in children and is frequently associated with neurofibromatosis type 1. These gliomas are usually pilocytic astrocytomas and cause fusiform enlargement of the nerve.

From the archives of the AFIP: Pediatric orbit tumors and tumorlike lesions: nonosseous lesions of the extraocular orbit.

The histologic spectrum of nonosseous tumors and tumorlike lesions of the extraocular orbit in children differs from that in adults, and the appearance of these lesions at imaging reflects their pathologic features. Rhabdomyosarcoma is the most common extraocular orbital tumor in children. This neoplasm usually manifests in young children, grows quite rapidly, and is fairly vascular. Vasculogenic lesions are common orbital lesions in newborns and young infants. The most prevalent of these are infantile hemangioma, a true neoplasm, and venous-lymphatic malformation, a developmental anomaly. Hemangioma is quite vascular, has a predictable course of proliferation followed by slow involution, and is distinguished on magnetic resonance images by the finding of flow voids within the mass and at its periphery. Venous-lymphatic malformation in the orbit is an anomaly of venous and lymphatic development that is characterized by unenhancing, cystic lymphatic and enhancing, solid venous components. Intralesional hemorrhage is common and frequently produces distinctive fluid-fluid levels within the cystic portions. Unlike hemangiomas, venous-lymphatic malformations grow with the patient and never involute spontaneously. Infantile fibromatosis is one of the fibromatoses and affects newborns and young infants. The tumor is nodular and composed of a zonal architecture, with frequent hemorrhage or necrosis in the central portion, characteristics that confer a target appearance at imaging. These lesions usually stop growing or spontaneously regress. All of these extraocular masses typically manifest with proptosis, and imaging differentiation is desirable because the treatments and prognoses vary greatly.