Comprehensive analysis of MYB/MYBL1-altered pediatric-type diffuse low-grade glioma.

BACKGROUND: Pediatric-type diffuse low-grade gliomas (pLGG) harboring recurrent genetic alterations involving MYB or MYBL1 are closely related tumors. Detailed treatment and outcome data of large cohorts are still limited. This study aimed to comprehensively evaluate pLGG with these alterations to define optimal therapeutic strategies. METHODS: We retrospectively reviewed details of pLGG with MYB or MYBL1 alterations from patients treated or referred for pathologic review at St. Jude Children's Research Hospital. Tumor specimens were centrally reviewed, and clinical data were collated. RESULTS: Thirty-three patients (18 male; median age, 5 years) were identified. Two tumors had MYBL1 alterations; 31 had MYB alterations, MYB::QKI fusion being the most common (n = 10, 30%). Most tumors were in the cerebral hemispheres (n = 22, 67%). Two patients (6%) had metastasis at diagnosis. The median follow-up was 6.1 years. The 5-year event-free survival (EFS) rate was 81.3% ±â€…8.3%; the 5-year overall survival (OS) rate was 96.4% ±â€…4.1%. Patients receiving a near-total or gross-total resection had a 5-year EFS of 100%; those receiving a biopsy or subtotal resection had a 5-year EFS rate of 56.6% ±â€…15.2% (P < .01). No difference in EFS was observed based on location, histology, or molecular alterations. However, the tumors that progressed or metastasized may have distinct methylation profiles with evidence of activation of the MAPK and PI3K/AKT/mTOR pathways. CONCLUSIONS: pLGG with MYB/MYBL1 alterations have good outcomes. Our findings suggest that surgical resectability is a crucial determinant of EFS. Further characterization is required to identify optimal treatment strategies for progressive tumors.

Static Magnetic Fields within Spinal Interbody Cages for the Promotion of Spinal Arthrodesis: A Pilot Study.

BACKGROUND: Spinal arthrodesis is a commonly performed spinal operation. Spinal arthrodesis can be complicated by pseudoarthrosis and resultant hardware failure. Static magnetic fields (SMF) have the ability to improve bone fusion. We seek to assess the feasibility of the construction and implantation of a lumbar interbody cage equipped with a SMF in a caprine model. METHODS: Six skeletally mature female Boer goats underwent a lateral approach for placement of an interbody graft at lumbar (L) 1-2 and 3-4. The goats were divided into 2 groups of 3 animals. The interbody graft contained a neodymium iron boron magnet in the experimental group and a nonmagnetic titanium sham in the control group. Both groups contained a synthetic bone graft. Blinded radiographic and histologic evaluation was performed at predetermined timepoints to assess degree of bony fusion and osseointegration. RESULTS: All 6 goats underwent successful placement of lumbar interbody grafts. At the 1-month postoperative computed tomography, 1 goat in the experimental group and 1 goat in the control group were noted to have dislodged their intervertebral cage. Qualitative radiographic and histologic evaluation identified enhanced bone formation, bone density, and osteointegration of the graft in the experimental group. CONCLUSIONS: A spinal interbody cage containing a neodymium iron boron magnet for the production of a local SMF is feasible. Preliminary data suggests enhanced bone formation, bone density, and osseointegration of the graft.

Progressive hypoventilation due to mixed CD8+ and CD4+ lymphocytic polymyositis following tremelimumab - durvalumab treatment.

BACKGROUND: The combination of CTLA-4 and PD-L1 inhibitors has a manageable adverse effect profile, although rare immune-related adverse events (irAE) can occur. CASE PRESENTATION: We describe an autoimmune polymyositis following a partial response to combination tremelimumab and durvalumab for the treatment of recurrent lung adenocarcinoma. Radiography revealed significant reduction in all metastases; however, the patient developed progressive neuromuscular hypoventilation due to lymphocytic destruction of the diaphragmatic musculature. Serologic testing revealed a low level of de novo circulating antibodies against striated muscle fiber. Immunohistochemistry revealed type II muscle fiber atrophy with a mixed CD8+ and CD4+ lymphocyte infiltrate, indicative of inflammatory myopathy. CONCLUSIONS: This case supports the hypothesis that muscle tissue is a target for lymphocytic infiltration in immune checkpoint inhibitor-associated polymyositis. Further insights into the autoimmune mechanism of PM will hopefully contribute to the prevention and treatment of this phenomenon.

Primary angiitis of the central nervous system presenting as unilateral optic neuritis.

A middle-aged woman who experienced recurrent episodes of unilateral vision loss and eye pain. On presentation, magnetic resonance imaging (MRI) demonstrated left optic nerve enhancement with patchy hyperintensities in the white matter of both frontal lobes and ill-defined enhancement in a lenticulostriate distribution. Ophthalmologic examination revealed left optic disc edema with a macular scar consistent with neuroretinitis. Her subsequent clinical course was notable for 2 episodes of painful vision loss, without associated neurologic symptoms, which resolved with intravenous and oral steroids. More than 1 year after her initial presentation, the patient developed right facial weakness and slurred speech, and shortly thereafter suffered a fatal intracerebral hemorrhage. Histopathology on autopsy confirmed a diagnosis of primary angiitis of the central nervous system (PACNS). This is an unusual case of PACNS presenting with recurrent unilateral optic neuritis. The vascular enhancement pattern on MRI suggesting inflamed cerebral blood vessels is a rarely described pattern, which likely reflects intracerebral extension of the ocular pathology. The combination of neuroretinitis and perivascular MRI enhancement pattern may represent a subtype of PACNS.

Intimal thickening of meningeal arteries after serial corticectomies for Rasmussen encephalitis.

Rasmussen encephalitis is a rare cause of intractable epilepsy in children. Between 2008 and 2010, 4 patients had second cortical resections performed after a primary corticectomy for Rasmussen encephalitis. In each case, we observed some degree of vessel wall change in leptomeningeal arteries, consisting of moderate to moderately severe intimal hyperplasia. The intervals between original resection and second operation ranged from 8 months to 10 years. Ages of the patients ranged from 9 to 12 years at their first resection and from 10 to 19 years at the time of revision. Four other Rasmussen encephalitis cases operated upon in the years 2006 to 2010 and 2 surgical revisions for severe cortical dysplasia, 1 for mild cortical dysplasia and 1 for recurrent dysembryoplastic neuroepithelial tumor, did not show significant vascular abnormalities (with surgical intervals of 10 months to 16 years). Leptomeningeal intimal hyperplasia appears to develop in the interval between repeated cortical resections for Rasmussen encephalitis, an inflammatory disorder. The pathogenesis of this vascular change may be related to meningeal inflammation in Rasmussen encephalitis. This finding in children undergoing surgical resection for Rasmussen encephalitis may itself lead to "secondary" ischemic change that contributes to worsening of epilepsy.

A case of black esophagus with histopathologic description and characterization.

Black esophagus, or acute necrotizing esophagitis, is a blackening of the esophagus that is usually distal with a sharp demarcation at the gastroesophageal border. Black esophagus is known to the gastroenterology community; however, to our knowledge it is virtually unknown in the pathology literature with only a single instance described in 1967. It is thought to occur as a poorly elucidated ischemic phenomenon. We report a case of black esophagus in a 45-year-old woman with a history of cocaine and alcohol abuse who was found unresponsive after a vague 2-day illness. On autopsy examination, the esophagus was black with ischemic necrosis of the mucosa, submucosa, and muscularis propria including a diffuse acute inflammatory infiltrate and brown pigmentation limited to the mucosa. Positive periodic acid-Schiff and negative iron stains suggest that the pigment is lipofuscin, likely secondary to ischemia.

A rare case of malignant pediatric ectomesenchymoma arising from the falx cerebri.

Malignant ectomesenchymoma is a rare tumor arising from mature ganglion cells with immature myogenous elements, with only 4 pediatric intracranial cases having been previously reported. The authors report a rare case of intracranial malignant ectomesenchymoma originating from the falx cerebri in a 10-year-old boy. The patient presented with a 2-week history of headache, nausea, and blurry vision, with mild lateral gaze diplopia. A CT scan revealed a solitary 7.2 × 3.8-cm dural-based mass that extended along the falx. No metastatic disease was identified, and the lesion was grossly resected without complication. Pathological investigation identified single and small groups of cells in a myxoid background, with polygonal or spindle-shaped cells containing eccentric nuclei and prominent nucleoli. Immunohistochemical staining of some cells was positive for smooth-muscle actin, CD99, and vimentin, whereas other cells (often process forming) were positive for S100 protein, synaptophysin, and neurofilament protein. Staining was negative for CD138, CD45, α-fetoprotein, CK AE1/3, glial fibrillary acidic protein, CK7, CK20, CD31, CD34, myoD, and desmin. Normal immunopositivity was seen for INI-1. The Ki 67 immunostaining had < 25% reactivity. The patient was treated with a sarcoma-based chemotherapy regimen and radiation to the craniospinal axis, and was found to be without recurrence or metastatic disease at 20 months.