Giant primary intracranial multi-fossa leiomyosarcoma involving the frontal sinus, ethmoid air cells, anterior fossa, middle fossa, and intraventricular space: A case report and literature review.

Background: Leiomyosarcomas (LMSs) is a type of sarcoma that arises from smooth muscle and generally presents in the abdomen. Although intracranial LMS has been identified before, most reported presentations have been in immunocompromised patients. Here, we present an intracranial LMS in an immunocompetent patient. Case Description: A 22-year-old male with a history of an atypical pineal parenchymal tumor of intermediate differentiation resected by suboccipital craniotomy at the age of 12 followed by adjuvant radiation therapy, presented with 3 weeks of decreased appetite, weight loss, and lethargy. He subsequently underwent transbasal approach skull base tumor resection. Histologic examination of the mass along with the patient's history of radiation was supportive of a low-grade, radiation-induced LMS arising from the anterior fossa of the skull or meninges and extends to the frontal sinus and ethmoid air cells. Conclusion: Primary intracranial LMS is an extremely rare diagnosis and presenting symptoms vary with the location and size of the tumor. Due to the poor specificity of clinical symptoms, diagnosis is often based on histology. The most common treatment is surgical resection. Adjuvant chemotherapy with various agents has been found to be somewhat effective outside the central nervous system. When LMS does occur, a history of immunocompromised state or previous radiation exposure is often present. Pathological confirmation is required for an appropriate diagnosis.

Leukostasis With Isolated Central Nervous System Involvement in Chronic Phase of Chronic Myelogenous Leukemia.

Chronic myelogenous leukemia (CML) is a hematologic malignancy with unique significance to the field of hematology and oncology, specifically due to the development of tyrosine kinase inhibitors (TKIs). CML often presents with nonspecific symptoms, and the quality of life in patients with CML has drastically improved as a result of TKIs. However, complications of CML including the risk of transforming into life-threatening blast crises continue to exist. Further, as most patients are asymptomatic in the chronic phase, patients often present with serious complications associated with noncompliance to TKIs. For example, central nervous system (CNS) manifestations of CML have been reported, both as the initial presentation of undiagnosed CML and as known complication of uncontrolled CML. Hyperleukocytosis is a manifestation of uncontrolled CML and leukostasis is a complication, occurring in cases of acute myeloid leukemia (AML). Here we present a rare case of leukostasis in a patient with known CML presenting on computed tomography (CT) as intracranial masses in the chronic phase. Our goal is to discuss this rare case of leukostasis in adult CML and describe its management.

Isocitrate Dehydrogenase Mutations Are Associated with Different Expression and DNA Methylation Patterns of OLIG2 in Adult Gliomas.

Isocitrate dehydrogenase (IDH) mutant gliomas are associated with a better prognosis in comparison to adult IDH wild-type glioma and glioma-CpG island methylator phenotypes. Although OLIG2 is mainly expressed in oligodendrocytes in normal adult brain, it is expressed in both astrocytomas and oligodendrogliomas. Utilizing the clinical, DNA methylation, and RNA-sequencing data from the Cancer Genome Atlas (TCGA) for lower-grade glioma and glioblastoma cohorts, we explored the association between IDH mutation status and OLIG2 expression on transcription, DNA methylation, and gene target levels. Compared to IDH wild-type gliomas, IDH mutant gliomas showed consistently higher expression of OLIG2 transcripts. OLIG2 overexpression is a good surrogate marker for IDH mutation with an AUC of 0.90. At the DNA methylation level, IDH-mutant gliomas showed hyper- and hypomethylation foci upstream of the OLIG2 transcription start site. Underexpressed OLIG2 target genes in IDH mutant glioma were enriched in cell cycle-related pathways. Thus, the differential expression of OLIG2 between IDH mutant and wild-type gliomas reflects involvement in multiple pathways in tumorigenesis.

Pediatric Temporal Lobe Meningioma With Meningioangiomatosis Mimicking Invasive Meningioma.

Meningiomas combined with meningioangiomatosis (MA-M) present similarly to more invasive lesions because of their appearance on neuroimaging. These lesions are especially rare in pediatric patients and suggestive imaging can help identify them for differential diagnosis. An 11-year-old male child who presented with diplopia and a headache was found to have an edematous invasive appearing temporal lobe mass on magnetic resonance imaging. Despite the lesion's appearance, it was completely resected and found to be a benign MA-M upon histopathologic examination. The present case demonstrated a rare meningioma with meningioangiomatosis that appeared to be a higher grade or invasive lesion upon initial imaging in a pediatric patient. A review of the literature was performed on patients who presented similarly. Despite the rarity of this condition in children, neuroimaging should be carefully examined prior to surgical resection of similar masses in preparation for highly vascular tissue, and post-operative course can be better anticipated when MA-M is considered during differential diagnosis.

SARS-CoV-2 vaccination induced cerebral venous sinus thrombosis: Do megakaryocytes, platelets and lipid mediators make up the orchestra?

The COVID-19 vaccines comprised of adenoviral vectors encoding the Spike (S) glycoprotein of SARS-CoV-2 are highly effective but associated with rare thrombotic complications. The adenovirus vector infects epithelial cells expressing the coxsackievirus and adenovirus receptor (CAR). The S glycoprotein expressed locally stimulates neutralizing antibody and cellular immune responses. These vaccines have been associated with thromboembolic events including cerebral venous sinus thrombosis (CVST). S glycoprotein stimulates the expression of cyclooxygenase-2 (COX-2) and leads to massive generation of thromboxane A2 in COVID-19. Megakaryocytes express CAR and we postulate that S glycoprotein stimulated generation of thromboxane A2 leads to megakaryocyte activation, biogenesis of activated platelets and thereby increased thrombogenicity. Cerebral vein sinuses express podoplanin, a natural ligand for CLEC2 receptors on platelets. Platelets traversing through the cerebral vein sinuses could be further activated by thromboxane A2-dependent podoplanin-CLEC2 signaling, leading to CVST. A prothrombotic hormonal milieu, and increased generation of thromboxane A2 and platelet activation in healthy females compared to males is consistent with increased risk for CVST observed in women. We propose that antiplatelet agents targeting thromboxane A2 receptor signaling such as low-dose aspirin merit consideration for chemoprophylaxis when administering the adenovirus based COVID-19 vaccines to young adults at risk of thrombosis provided there are no contraindications.

Aggressive FUS-Mutant Motor Neuron Disease Without Profound Spinal Cord Pathology.

A 29-year-old man presented with rapidly progressive severe neck weakness, asymmetrical bilateral upper extremity weakness, bulbar dysfunction, profound muscle wasting, and weight loss. Within 1 year, his speech became unintelligible, he became gastrostomy- and tracheostomy/ventilator-dependent, and wheelchair bound. Electrophysiology suggested motor neuron disease. Whole exome sequencing revealed a heterozygous pathogenic variant in the fused in sarcoma gene (FUS), c.1574C>T,p. R525L, consistent with autosomal dominant amyotrophic lateral sclerosis. Autopsy revealed extensive denervation atrophy of skeletal musculature. Surprisingly, there was only minimal patchy depletion of motor neurons within the cervico-thoracic spinal cord anterior horn cells, and the tracts were largely preserved. TDP-43 inclusions were absent. Abnormal expression of FUS mutation product (cytoplasmic inclusions) was demonstrated by immunohistochemistry within anterior horn motor neurons. The most prominent finding was a disparity between profound neck weakness and relatively low-grade anterior horn cell loss or tract degeneration in the cervico-thoracic cord.

Proteomic Analysis of Mouse Brain Subjected to Spaceflight.

There is evidence that spaceflight poses acute and late risks to the central nervous system. To explore possible mechanisms, the proteomic changes following spaceflight in mouse brain were characterized. Space Shuttle Atlantis (STS-135) was launched from the Kennedy Space Center (KSC) on a 13-day mission. Within 3⁻5 h after landing, brain tissue was collected to evaluate protein expression profiles using quantitative proteomic analysis. Our results showed that there were 26 proteins that were significantly altered after spaceflight in the gray and/or white matter. While there was no overlap between the white and gray matter in terms of individual proteins, there was overlap in terms of function, synaptic plasticity, vesical activity, protein/organelle transport, and metabolism. Our data demonstrate that exposure to the spaceflight environment induces significant changes in protein expression related to neuronal structure and metabolic function. This might lead to a significant impact on brain structural and functional integrity that could affect the outcome of space missions.

Acquired factor VII deficiency causing severe bleeding disorder secondary to AL amyloidosis of the liver.

A 52 year-old male presented with neck pain after undergoing thyroidectomy for a goiter three weeks prior which was complicated by a neck hematoma requiring evacuation. Computed tomography (CT) scan showed a neck hematoma requiring evacuation and he received desmopressin with cessation of bleeding. Coagulation studies were normal. He returned eighteen months later with severe oral mucosal bleeding after a dental procedure and required transfusions with red blood cells, platelets, and fresh frozen plasma (FFP) in addition to desmopressin, Humate-P, aminocaproic acid, and surgical packing. A comprehensive bleeding diathesis workup was normal. He was readmitted six months later due to abdominal pain and distention and found to have massive hepatosplenomegaly on CT. A new coagulopathy workup revealed prolonged INR to 1.5, corrected prothrombin time mixing study, and a low factor VII level (29%), suggesting acquired factor VII deficiency. A transjugular liver biopsy revealed extensive involvement by ALamyloidosis- Kappa type. He then developed a large right retroperitoneal hematoma which required multiple transfusions with FFP, cryoprecipitate, aminocaproic acid, and vitamin K with slight success. Hemorrhage was subsequently stabilized with recombinant factor VIIa administered every four hours which corresponded with correction of factor VII levels and PT and eventual cessation hemorrhage. Acquired factor VII deficiency causing severe coagulopathy was attributed to hepatic amyloidosis ALkappa subtype. We started treatment with bortezomib, dexamethasone, and cyclophosphamide, however, the patient succumbed to uncontrolled hemorrhage. Acquired factor VII deficiency is extremely rare and to our knowledge, this is the only known case of factor VII deficiency secondary to amyloidosis involving the liver.

Epilepsy Surgery for Skull-Base Temporal Lobe Encephaloceles: Should We Spare the Hippocampus from Resection?

The neurosurgical treatment of skull base temporal encephalocele for patients with epilepsy is variable. We describe two adult cases of temporal lobe epilepsy (TLE) with spheno-temporal encephalocele, currently seizure-free for more than two years after anterior temporal lobectomy (ATL) and lesionectomy sparing the hippocampus without long-term intracranial electroencephalogram (EEG) monitoring. Encephaloceles were detected by magnetic resonance imaging (MRI) and confirmed by maxillofacial head computed tomography (CT) scans. Seizures were captured by scalp video-EEG recording. One case underwent intraoperative electrocorticography (ECoG) with pathology demonstrating neuronal heterotopia. We propose that in some patients with skull base temporal encephaloceles, minimal surgical resection of herniated and adjacent temporal cortex (lesionectomy) is sufficient to render seizure freedom. In future cases, where an associated malformation of cortical development is suspected, newer techniques such as minimally invasive EEG monitoring with stereotactic-depth EEG electrodes should be considered to tailor the surrounding margins of the resected epileptogenic zone.

Propionibacterium acnes-associated neurosarcoidosis: A case report with review of the literature.

A 56-year-old woman with a 3-year history of hydrocephalus and ventriculo-peritoneal shunt placement, presented with worsening altered level of consciousness for 2 days. Imaging studies showed severe ventriculomegaly involving the lateral and third ventricles with multiple septated cysts noted in the lateral ventricles predominantly near the frontal horns. Histopathologic examination of the excised brain lesion revealed choroid plexus tissue and adjacent cerebral parenchyma with several non-caseating granulomas. Granulomatous inflammation was also identified in mediastinal lymph nodes. By using specific monoclonal antibodies, Propionibacterium acnes (P. acnes) were detected in non-caseating granulomas of both the brain and mediastinal lymph nodes. No acid-fast bacilli or fungal elements were present. To the best of our knowledge, this is the first demonstration of P. acnes in sarcoid granulomas of cerebral tissue, and it reinforces the possible link between P. acnes and sarcoidosis.

Rare Intradural Cervical Nerve Root Metastasis of Follicular Thyroid Carcinoma.

Intradural extramedullary nerve root metastasis is extremely unusual with only a handful of cases reported, and it presents most commonly in the thoracic and lumbosacral regions. We report the first case of metastasis to a ventral cervical nerve root in a patient with low-grade follicular thyroid carcinoma thought to be in remission for several years. Histopathology demonstrated malignant transformation and invasion of the nerve root. This case underscores that any history of malignancy regardless of staging, grading, or remission status should raise the suspicion of metastasis as it can mimic other spine and nerve sheath tumors and represent malignant transformation. Gross total resection can be safely achieved with intraoperative neuromonitoring and result in improved function; however, treatment is likely palliative.

Treatment of IgG4-related pachymeningitis in a patient with steroid intolerance: The role of early use of rituximab.

IgG4-related pachymeningitis is a serious inflammatory condition that can present with symptoms of mass effect and focal deficits. The first-line therapy is steroids and second-line is chemotherapy (methotrexate, azathioprine, etc.). We describe a patient with IgG4-related pachymeningitis in whom steroid use was contraindicated and methotrexate was ineffective. During the course of treatment, the patient presented to the emergency department with receptive and expressive aphasia, slurred speech, right-sided neglect, and loss of sensation. After a single infusion of rituximab and anticonvulsants, her symptoms resolved. Our unique case suggests that patients with IgG4-related pachymeningitis might benefit from early initiation of rituximab.

Pyloric gland adenoma of gallbladder-reports of two cases and a brief review of literature.

Adenomas of the gallbladder are uncommon benign epithelial neoplasms. Rarely, they can give rise to gallbladder cancer, which is the most common malignancy of the biliary tract, carrying a poor prognosis and decreased survival. Here we report the case histories of two patients, 40-year-old and 53-year-old males who presented with >1 cm gallbladder polyps, which were detected and confirmed using various imaging studies. Cholecystectomy was performed on both patients and the subsequent pathologic exam revealed 1.2 and 1.6 cm polyps in the lumen. Histopathologically, both polyps showed features reminiscent of "pyloric" gland type of adenoma. The differences between the two cases in regard to histopathological and immunohistochemical characteristics will be discussed. We will also briefly review the latest nomenclature on such low-grade polypoid gallbladder entities.

Acute Postviral Encephalopathy: Pathologic and Radiologic Correlation in an Atypical Case.

The authors report a case of fatal acute encephalopathy following influenza infection, with slightly atypical pathological and imaging findings. A healthy 8-year-old boy with probable recent influenza A/B infection admitted for refractory seizures was placed on phenobarbital coma and later developed hemodynamic instability. Magnetic resonance imaging revealed bilateral cerebral and cerebellar white matter lesions and microhemorrhages. Following his demise, the autopsy revealed a large area of necrosis in the right centrum semiovale with similar lesions in the temporal and cerebellar regions. Microscopically, there was extensive coagulative necrosis, compatible with necrotizing white matter encephalopathy, and neuronal loss suggesting superimposed hypoxic-ischemia. The acute progressive neurologic deterioration was partly reminiscent on acute necrotizing encephalopathy, a condition recently associated with influenza A. In acute necrotizing encephalopathy, typical brain findings are characterized by bilateral thalamic necrosis/petechiae with variable white matter edema. The somewhat atypical findings in our case can relate to superadded cardiovascular collapse and hypoxic-ischemic effects.

Evaluation of phytochemical-incorporated porous polymeric sponges for bone tissue engineering: a novel perspective.

Porous polymeric scaffolds are extensively studied for delivery of bone growth factors. Since phytochemicals are known to produce changes in cell signalling and other metabolic pathways, osteogenic phytochemicals, that is, extracts of Cissus quadrangularis and Butea monosperma, are incorporated into sulphonated poly(aryl ether ketone) sponges. The results have shown that the scaffolds with phytochemicals enhanced the proliferation and alkaline phosphatase activity of the cells compared to cells treated on scaffolds without phytochemicals. Hence, these phytochemicals can be evaluated to augment, if not substitute the use of bone morphogenetic proteins in scaffolds.

Analysis of light scattering from human breast tissue using a custom dual-optical scanning near-field optical microscope.

In this paper we introduce a custom scanning near-field optical microscope (SNOM) that simultaneously collects reflection and transmission near-field images along with topography. This dual-optical SNOM uses a bent probe, which allows for axial reflection imaging, accurate surface scanning, and easy identification of topographic artifacts. Using this novel dual-optical SNOM, we image desiccated and non-desiccated human breast epithelial tissue. By comparing the simultaneous SNOM images, we isolate the effects of tissue morphology and variations in refractive indices on the forward- and back-scattering of light from the tissue. We find that the reduction in back-scattering from tissue, relative to the glass slide, is caused by dense packing of the scattering sites in the cytoplasm (morphology) in the desiccated tissue and a thin-film of water adhering to the glass slide (refractive index) in the non-desiccated tissue sample. Our work demonstrates the potential of our customized dual-optical SNOM system for label-free tissue diagnostics.

Nearly identical near-haploid karyotype in a peritoneal mesothelioma and a retroperitoneal malignant peripheral nerve sheath tumor.

The presence of a near-haploid karyotype is a rare finding in human malignancies, most frequently occurring in acute leukemia. In solid tumors, a near-haploid karyotype has been reported in fewer than 40 cases. We report two nearly identical near-haploid karyotypes from two distinctly different tumor types. The first case is a biphasic malignant mesothelioma from a 53-year-old white woman forming a large retroperitoneal mass. Cytogenetic evaluation revealed a primary hyperdiploid cell population as well as near-haploid and hypertetraploid populations with an overall karyotype of 27,XX,i(5)(p10),+7,add(15)(p11.2),+dic(1;20)(p13;p13)[2]/54,idemx2[90]/101-108,idemx4[19]. The second case is a large pelvic mass from a 48-year-old man. Histologic examination identified a malignant peripheral nerve sheath tumor displaying a karyotype of 26,X,+i(5)(p10),+7,der(15)t(1;15)(q12;p12),+20[5]/52,idemx2[20]. Herein we discuss the potential relationship between these two disparate neoplasms with nearly identical near-haploid karyotypes and present a literature review.

Pineal anlage tumor in a 5-month-old boy.

Pineal tumors are rare neoplasms that are categorized into pineoblastomas, pineocytomas, and pineal parenchymal tumors of intermediate differentiation. Pineal anlage tumors are primary pineal tumors with neuroepithelial and ectomesenchymal differentiation and without endodermal differentiation. The authors review the literature and report the case of a 5-month-old boy with a pineal anlage tumor. This is only the sixth case of a pineal anlage tumor reported in the English-language literature adding to the understanding of this tumor's presentation, immunomorphological and molecular characteristics, embryological origin, radiological appearance, treatment outcome, and prognosis.