Neuropathology : Official Journal of the Japanese Society of Neuropathology

ALK-positive histiocytosis is a rare histiocytic disease characterized by ALK positivity. It was first described in 2008 as a systemic disease in infants. The disease often shows positivity for CD68 and CD163 on immunohistochemistry, and genomic analysis frequently reveals KIF5B::ALK fusions. ALK-positive histiocytosis typically follows an indolent course and has a promising prognosis, with conventional treatments usually being effective. Here, we report a rare case of ALK-positive histiocytosis with exclusive involvement of the central nervous system in a 33-year-old Asian adult woman...

We report an autopsy case of a 70-year-old man who was clinically diagnosed with atypical progressive supranuclear palsy (PSP). He initially presented with gait ataxia and then showed vertical gaze palsy, rigidity, akinesia, dysphagia, and mild cognitive impairment, followed by prominent upper motor signs later in the course of the disease. Cranial magnetic resonance imaging revealed tegmental atrophy of the midbrain. Autopsy revealed severe neuronal loss and gliosis in the motor cortex and corticospinal degeneration and mild to moderate neuronal loss and gliosis in the basal ganglia, substantia nigra, midbrain, and pons...

N-myc downstream regulated gene 1 (NDRG1) is a member of the NDRG family, of which four members (NDRG1, NDRG2, NDRG3, and NDRG4) have been identified. NDRG1 is repressed by c-MYC and N-MYC proto-oncogenes. NDRG1 is translated into a 43 kDa protein that is associated with the regulation of cellular stress responses, proliferation, and differentiation. In this study, we aimed to clarify the relationship between progression of glioblastoma (GB) IDH-wildtype and NDRG1 expression in tumor cells. We assessed the expression of NDRG1 in 41 GBs using immunostaining and evaluated its prognostic significance...

Eosinophilic angiocentric fibrosis (EAF) is a rare, benign fibroinflammatory condition primarily affecting the sinonasal and upper respiratory tract, with a few cases reported beyond these regions. Primary intracranial EAF is rare. To date, only one case of intracranial EAF has been reported; ours is the second. This case report presents a case of EAF in a 55-year-old man, initially misdiagnosed as meningioma based on clinical and radiological features. The patient complained of a persistent dull headache for six months without associated neurological symptoms...

A 55-year-old Japanese woman with a history of hypertension and right putaminal hemorrhage developed simultaneous hemorrhages in the left thalamus and putamen and died 24 h later. There were no vascular anomalies in the brain. Synaptophysin immunostaining combined with eosin azure 50 (EA50) staining clearly identified the hematoma and the surrounding brain structures. In the right cerebral hemisphere, a cystic lesion as a sequela of the usual type of hypertensive putaminal hematoma was evident. In the left cerebral hemisphere, two fresh hematomas were evident...

The 2021 World Health Organization (WHO) classification of the central nervous system (CNS) tumors has classified diffuse leptomeningeal glioneuronal tumor (DLGNT) as a mixed neuronal and glial tumor. Here, we report a DLGNT with two distinct morphological tumor components but identical molecular features. A four-year-old female child presented with progressive right upper extremity weakness. Magnetic resonance imaging (MRI) revealed the leptomeningeal enhancement over the brain stem and cervicothoracic spine...

Dystrophinopathy is caused by alterations in the dystrophin gene. The severe phenotype, Duchenne muscular dystrophy (DMD), is caused by a lack of dystrophin in skeletal muscles, resulting in necrosis and regenerating fibers, inflammatory cells, and muscle fibrosis. Progressive muscle weakness is a characteristic finding of this condition. Here, we encountered a rare case of a 10-year-old patient with asymptomatic dystrophinopathy with no dystrophin expression and investigated the reason for the absence of muscle weakness to obtain therapeutic insights for DMD...

The first postmortem neuropathological findings of a hemiparkinsonism and hemiatrophy (HPHA) patient are presented. A 50-year-old man developed resting tremors affecting the right hand and leg, followed by mild clumsiness of the right hand. On examination, he exhibited muscle atrophy of the right leg extremity, accompanied by right-sided parkinsonism. Brain magnetic resonance imaging was normal. Based on the clinical and radiological findings, HPHA syndrome was diagnosed, showing a good response to L-DOPA. He gradually developed muscular atrophy of the right distal upper extremity...

Glycogen storage diseases (GSDs) are a group of metabolic disorders affecting glycogen metabolism, with polyglucosan body myopathy type 1 (PGBM1) being a rare variant linked to RBCK1 gene mutations. Understanding the clinical diversity of PGBM1 aids in better characterization of the disease. Two unrelated Iranian families with individuals exhibiting progressive muscle weakness underwent clinical evaluations, genetic analysis using whole exome sequencing (WES), and histopathological examinations of muscle biopsies...

Multiple sclerosis (MS), the leading cause of disability in young adults, is an inflammatory disease of the central nervous system characterized by localized areas of demyelination. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been shown to be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Interestingly, ASK1 signaling regulates glial cell interactions and drives neuroinflammation in EAE mice...

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MBSHH , 13.0% MBWNT , 7.3% MBGrp3 , and 13...

A 68-year-old woman presented with difficulty finding words and writing characters. Neurological examination led to clinical diagnosis at onset of the logopenic variant of primary progressive aphasia accompanied with ideomotor apraxia, visuospatial agnosia on the right, and Gerstmann syndrome. Bradykinesia and rigidity on the right with shuffling gait developed after one year. Treatment with L-dopa had no effect. The patient was diagnosed with corticobasal syndrome (CBS). Brain magnetic resonance imaging revealed diffuse cortical atrophy dominantly on the left, especially in the temporal, parietal, and occipital lobes...

In the evolving landscape of ependymoma classification, which integrates histological, molecular, and anatomical context, we detail a rare case divergent from the usual histopathological spectrum. We present the case of a 37-year-old man with symptomatic spinal cord compression at the L3-L4 level. Neuroradiological evaluation revealed an intradural, encapsulated mass. Histologically, the tumor displayed atypical features: bizarre pleomorphic giant cells, intranuclear inclusions, mitotic activity, and a profusion of eosinophilic cytoplasm with hyalinized vessels, deviating from the characteristic perivascular pseudorosettes or myxopapillary patterns...

An 84-year-old man presented with somnolence, dysphagia, and right hemiplegia, all occurring within a month, approximately one year after initial admission due to subacute, transient cognitive decline suggestive of acute disseminated encephalomyelitis involving the cerebral white matter. Serial magnetic resonance imaging (MRI) studies over that period revealed three high-intensity signal lesions on fluid-attenuated inversion recovery images, appearing in chronological order in the left upper and left lower medulla oblongata and left pontine base...

In 2016, the World Health Organization (WHO) eliminated "oligoastrocytoma" from the classification of central nervous system (CNS) tumors, in favor of an integrated histologic and molecular diagnosis. Consistent with the 2016 classification, in the 2021 classification, oligodendrogliomas are defined by mutations in isocitrate dehydrogenase (IDH) with concurrent 1p19q codeletion, while astrocytomas are IDH mutant tumors, usually with ATRX loss. In 2007, a 24-year-old man presented with a brain tumor histologically described as astrocytoma, but with molecular studies consistent with an oligodendroglioma, IDH mutant and 1p19q-codeleted...

The hypothalamus is the region of the brain that integrates the neuroendocrine system and whole-body metabolism. Patients with Alzheimer's disease (AD) have been reported to exhibit pathological changes in the hypothalamus, such as neurofibrillary tangles (NFTs) and amyloid plaques (APs). However, few studies have investigated whether hypothalamic AD pathology is associated with clinical factors. We investigated the association between AD-related pathological changes in the hypothalamus and clinical pictures using autopsied brain samples obtained from deceased residents of a Japanese community...

Argyrophilic grain disease (AGD) is one of the major pathological backgrounds of senile dementia. Dementia with grains refers to cases of dementia for which AGD is the sole background pathology responsible for dementia. Recent studies have suggested an association between dementia with grains and parkinsonism. In this study, we aimed to present two autopsy cases of dementia with grains. Case 1 was an 85-year-old man who exhibited amnestic dementia and parkinsonism, including postural instability, upward gaze palsy, and neck and trunk rigidity...

Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA-binding protein of 43 kDa (TDP-43) accumulation. Here we report the autopsy findings of a 64-year-old right-handed man with an atypical TDP-43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen...

The mutations of the feline leukemia virus subgroup C receptor-related protein 1 (FLVCR1) cause ataxia with retinitis pigmentosa. Recent studies indicated a large variation in the phenotype of FLVCR1-associated diseases. In this report, we describe an adult male who manifested first with tremors in his third decade, followed by retinitis pigmentosa, sensory ataxia, and sensory neuropathy in his fourth decade. While retinitis pigmentosa and sensory ataxia are well-recognized features of FLVCR1-associated disease, tremor is rarely described...

We present a comprehensive characterization of clinical, neuropathological, and multisystem features of a man with genetically confirmed McLeod neuroacanthocytosis syndrome, including video and autopsy findings. A 61-year-old man presented with a movement disorder and behavioral change. Examination showed dystonic choreiform movements in all four limbs, reduced deep-tendon reflexes, and wide-based gait. He had oromandibular dyskinesia causing severe dysphagia. Elevated serum creatinine kinase (CK) was first noted in his thirties, but investigations, including muscle biopsy at that time, were inconclusive...