Neuropathology最新文献

Diagnosis of lymphomatosis cerebri (LC) is usually delayed because of its rarity and the need for pathological confirmation. The association of LC with humoral immunity has scarcely been reported. Herein, we present a woman with a 2-week history of dizziness and gait ataxia, followed by diplopia, altered mental status, and spasticity of all limbs. Magnetic resonance imaging (MRI) of the brain showed multifocal lesions involving bilateral subcortical white matter, deep gray structures, and brainstem. Oligoclonal bands and anti-N-methyl-D-aspartate receptor (NMDAR) antibodies were present in cerebrospinal fluid (CSF) twice. She was initially treated with methylprednisolone but still worsening. A stereotactic brain biopsy confirmed the diagnosis of LC. This is a report on the distinctive coexistence of the rare CNS lymphoma variant and the anti-NMDAR antibody.

Pilocytic astrocytoma (PA), a central nervous system (CNS) World Health Organization grade 1 tumor, is mainly seen in children or young adults aged 5-19. Surgical resection often provides excellent outcomes, but residual tumors may still remain. This low-grade tumor is well recognized for its classic radiological and morphological features; however, some unique molecular findings have been unveiled by the application of next-generation sequencing (NGS). Among the genetic abnormalities identified in this low-grade tumor, increasing evidence indicates that BRAF alterations, especially BRAF fusions, play an essential role in PA tumorigenesis. Among the several fusion partner genes identified in PAs, KIAA1549-BRAF fusion is notably the most common detectable genetic alteration, especially in the cerebellar PAs. Here, we report a case of a young adult patient with a large, right-sided posterior fossa cerebellar and cerebellopontine angle region mass consistent with a PA. Of note, NGS detected a novel GNAI3-BRAF fusion, which results in an in-frame fusion protein containing the kinase domain of BRAF. This finding expands the knowledge of BRAF fusions in the tumorigenesis of PAs, provides an additional molecular signature for diagnosis, and a target for future therapy.

Molecular alterations nowadays play a crucial role in the diagnosis of brain tumors. Some of these alterations are associated with outcome and/or response to treatment, including sequence variants of isocitrate dehydrogenase (IDH) at position p.R132 or p.R172. Such IDH variants have so far been described in histone H3-wildtype primary brain tumors only in adult-type diffuse gliomas and are associated with a better outcome compared to their IDH-wildtype counterpart, the glioblastoma. Moreover, homozygous loss of CDKN2A and/or CDKN2B in IDH-mutant astrocytomas shortens the median overall survival regardless of histological features of malignancy. Such tumors are therefore considered to be aggressive and graded as WHO central nervous system (CNS) grade 4 lesions. The coexistence of an IDH-sequence variation and a BRAF p.V600E alteration has only rarely been described in diffuse astrocytomas. Due to the small number of cases, little is known about such neoplasms in terms of clinical behavior and response to treatment. Herein we describe the first case, to our knowledge, of an astrocytoma (CNS WHO grade 4), IDH-mutant, and BRAF p.V600E-mutant with homozygous deletion of CDKN2A. Pathologists should be aware that such an expression profile does exist even in WHO CNS grade 4 astrocytomas, IDH-mutant, and are encouraged to test for the BRAF p.V600E sequence variant as such an alteration may provide additional treatment options.

Cerebral ischemia may lead to axonal injury not only at the site of the primary lesion but also in a region remote to the site of insult. In this study, we investigated the effect of herniation on the development of axonal injury at a site remote to the primary lesion during the acute phase of cerebral ischemia. We obtained postmortem brains of 13 cases with acute phase of unilateral cerebral infarction in the territory of the internal carotid artery or middle cerebral artery and seven controls. We classified the brain tissues into herniation and non-herniation groups. Then we examined whether axonal and ischemic changes existed in the corpus callosum contralateral to the ischemic hemisphere and the upper pons. In the herniation group, we detected white-matter lesions by Klüver-Barrera staining, microglial loss by immunohistochemistry for ionized calcium-binding adaptor molecule 1, and axonal injury by immunohistochemistry for amyloid precursor protein. However, none of the aforementioned findings were observed in the non-herniation group. These findings suggest the existence of regional overlap in axonal and ischemic pathologies in remote regions in the presence of herniation. We concluded that herniation may play a significant role in the development of axonal and ischemic changes in the remote region. Our results suggest that axonal injury in a remote region may result from expanded ischemic lesions due to herniation.

A 65-year-old woman with a resolved history of epilepsy due to a motor vehicle accident and hippocampal sclerosis presented with recurrent de novo seizures. Brain imaging demonstrated enhancement in the left parieto-occipital lobe. At histopathological examination, the lesion displayed a diffuse lymphoid infiltrate comprised of small atypical lymphocytes, plasmacytoid lymphocytes, and scattered plasma cells with amyloid deposition. Pathology workup demonstrated a monotypic B-cell phenotype of the lymphoid infiltrate, expressing lambda light chain restriction and plasmacytic differentiation without MYD88 mutations. The patient had no systemic evidence of lymphoma, plasma cell dyscrasia, or amyloidosis. A diagnosis of low-grade B-cell lymphoma of the central nervous system with plasmacytic differentiation and amyloid deposition was made.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by extensive heterotopic ossification of soft tissue structures leading to severe limitations in movement. FOP is caused by a germline mutation in the activating receptor type IA (ACVR1) gene. Worrisome is the fact that up to a third of diffuse intrinsic pontine gliomas (DIPG) also harbor the same point mutation in ACVR1. Radiological reports of central nervous system (CNS) involvement by FOP have described brainstem masses; however, the literature on the histopathology or pathogenesis of these lesions is scant. Here we present detailed neuropathologic findings of a brainstem mass in a patient with FOP and suggest that the tumor is hamartomatous in nature. This report, along with a literature review of radiographic and laboratory data, offers support for the idea that the ACVR1 mutation may incite CNS proliferation, predominantly in the brainstem, but is probably not an oncologic driver. These lesions may be seen at autopsy and are likely noncontributory to death.

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY), one of the pediatric-type diffuse low-grade gliomas, is characterized by a diffuse infiltrating pattern of oligodendroglioma-like tumor cells showing CD34 positivity and harbors mitogen-activated protein kinase (MAPK) alteration, such as vRAF murine sarcoma viral oncogene homolog B1 (BRAF) p.V600E or fibroblast growth factor fusion genetically. It occurs mainly in pediatric and adolescents with seizures due to the dominant location of the temporal lobe. However, there have been a few cases of PLNTY in adult patients, suggesting the wide range of this tumor spectrum. Here, we describe two cases of PLNTY, one in a 14-year-old female and the other in a 66-year-old female. The pediatric tumor showed typical clinical course and histopathology with BRAF p.V600E mutation, whereas the elderly tumor was unusual because of non-epileptic onset clinically and ependymal differentiation histopathologically harboring KIAA1549-BRAF fusion. There might be unusual but possible PLNTY, as in our elderly case. We also compared typical pediatric and unusual elderly tumors by reviewing the literature.

MGMT promoter methylation status can change in response to several factors, treatment with alkylating therapy being the mechanism more commonly cited in the literature. Some authors have attempted to quantify these alterations, with inconsistent results. This study aims to determine changes in MGMT promoter methylation status by pyrosequencing, which quantitatively yields results, in a cohort of patients reoperated for recurrent glioblastoma and having previously completed the Stupp protocol. Methylation status of the MGMT promoter gene of a total of 24 pairs of glioblastoma preselected tumor samples was retrospectively analyzed using pyrosequencing and depicted as percentages or categories (hypermethylated, intermediate methylation, unmethylated). Matched samples were compared using Wilcoxon signed-rank test, and log-rank test was used to establish a correlation with survival data. The median value of MGMT promoter methylation status declined after adjuvant treatment from 20.35% to 14.25% (p = 0.346). A significant correlation between methylation in primary samples and overall survival (p = 0.05) and progression-free survival (p = 0.024) was found. Intermediate methylation status at recurrence was linked to greater survival after progression, without reaching statistical significance (post-progression survival [PPS]) (p = 0.217). Although treatment with alkylating chemotherapy was a common feature in all patients of our cohort, switching in both directions was observed when MGMT promoter methylation status was analyzed as a continuous variable. These data suggest that the dynamics of epigenetics may be very complex and not entirely explained by clonal selection influenced by temozolomide.

We report an autopsy case of progressive supranuclear palsy (PSP-Richardson syndrome). The individual had been enrolled in a phase 2 trial and received a monoclonal tau antibody (tilavonemab, ABBV-8E12); he died of intrahepatic cholangiocarcinoma and gastrointestinal bleeding during the clinical trial. Neuropathological examination demonstrated neuronal loss, gliosis, and widespread deposits of phosphorylated tau in the neurofibrillary tangles, tufted astrocytes, coiled bodies, and threads, which mainly occurred in the inferior olive nucleus, dentate nucleus of the cerebellum, substantia nigra, midbrain tegmentum, subthalamic nuclei, globus pallidus, putamen, and precentral gyrus, confirming typical PSP pathology. Phosphorylated tau was also found to accumulate in Betz cells, Purkinje cells, and pencil fibers in the basal ganglia. In conclusion, no additional changes or pathological modifications, which were expected from immunotherapy targeting tau, were visible in the present case.