Neuropathology最新文献

{"title":"Clinicopathological study of dementia with grains presenting with parkinsonism compared with a typical case.","authors":"Akira Arakawa, Ryoji Goto, Mana Higashihara, Yuko Hiroyoshi, Ayako Shioya, Manato Hara, Makoto Orita, Tomoyasu Matsubara, Renpei Sengoku, Masashi Kameyama, Aya M Tokumaru, Masato Hasegawa, Tatsushi Toda, Atsushi Iwata, Shigeo Murayama, Yuko Saito","doi":"10.1111/neup.12973","DOIUrl":"10.1111/neup.12973","url":null,"abstract":"<p><p>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. The patient was clinically diagnosed with progressive supranuclear palsy and Alzheimer's disease. Case 2 was a 90-year-old man with pure amnestic dementia, clinically diagnosed as Alzheimer's disease. Recently, we used cryo-electron microscopy to confirm that the tau accumulated in both cases had the same three-dimensional structure. In this study, we compared the detailed clinical picture and neuropathological findings using classical staining and immunostaining methods. Both cases exhibited argyrophilic grains and tau-immunoreactive structures in the brainstem and basal ganglia, especially in the nigrostriatal and limbic systems. However, Case 1 had more tau immunoreactive structures. Considering the absence of other disease-specific structures such as tufted astrocytes, astrocytic plaques and globular glial inclusions, lack of conspicuous cerebrovascular disease, and no history of medications that could cause parkinsonism, our findings suggest an association between AGD in the nigrostriatal system and parkinsonism.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"376-387"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collision tumor: Multinodular and vacuolating neuronal tumor with isocitrate dehydrogenase-mutant diffuse astrocytoma.","authors":"Vinodh A Kumar, Alejandro Perez, Angela L Young, Julia Jones, Barbara J O'Brien, Frederick F Lang, Jason T Huse, Gregory N Fuller","doi":"10.1111/neup.12968","DOIUrl":"10.1111/neup.12968","url":null,"abstract":"<p><p>Herein, we report a case of a collision tumor involving a multinodular and vacuolating neuronal tumor (MVNT) and a diffuse astrocytoma. A collision tumor between these two entities has not previously been reported. The patient is a 35-year-old woman who presented with new-onset hearing loss and ringing in her right ear. Magnetic resonance imaging identified a non-enhancing mass involving the gray matter and subcortical white matter of the left middle frontal gyrus. Additionally, tiny clustered nodules were noted along the underlying subcortical ribbon and superficial subcortical white matter of the left superior frontal gyrus. The patient underwent a left frontal craniotomy and complete resection of the mass. Histologic examination of the resected specimen demonstrated a collision tumor consisting of a diffuse astrocytoma (isocitrate dehydrogenase [IDH] mutant, central nervous system [CNS] World Health Organization [WHO] grade 2) and an MVNT, with the latter demonstrating characteristic morphologic and immunohistochemical features.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"333-337"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Rosai-Dorfman disease of the central nervous system: A clinical, histological, and molecular appraisal.","authors":"Mayur Parkhi, Debajyoti Chatterjee, Dharambir Kashyap, Ashish Aggarwal, Bishan Radotra","doi":"10.1111/neup.12972","DOIUrl":"10.1111/neup.12972","url":null,"abstract":"<p><p>Rosai-Dorfman disease (RDD) is characterized by clonal proliferation of S-100 positive histiocytes and variable emperipolesis. It commonly affects cervical lymph nodes. Central nervous system (CNS) involvement is extremely rare. We attempted to evaluate the Cyclin D1 expression and frequency of KRAS and BRAF mutations in the RDD involving the CNS. All patients with histopathologically diagnosed RDD involving CNS were recruited from 2011 to 2022. All cases were subjected to immunohistochemistry for CD68, CD163, S100, CD1a, GFAP, CD207, EMA, ALK, BRAFV600E, IgG4, IgG, and CyclinD1. The real-time polymerase chain reaction (RT-PCR) for hotspot mutation analysis of KRAS (exons 2, 3, and 4) and BRAF (V600E) was conducted on formalin-fixed paraffin-embedded tissue using a commercial kit (EntroGen). A total of seven cases were included. The median age was 31 years, with six men and one woman. It showed spinal cord (n = 4) and intracranial (n = 3) involvement. Histologically, all cases showed histiocyte-rich inflammation with evidence of emperipolesis. These histiocytes were positive for S100, CD68, CD163, and Cyclin D1, whereas negative for CD1a, CD207, and EMA. BRAF V600E was expressed in a single case. None of the control cases (demyelination and infarction) with histiocytic infiltrate showed Cyclin D1 expression. Four RDD cases showed increased IgG4-positive plasma cells (>10/HPF) and IgG4/IgG ratio (>40%). BRAF V600E mutation was detected in one case (14.28%), while none showed KRAS mutation. RDD involving CNS is extremely rare and diagnostically challenging. Nuclear Cyclin D1 expression along with S-100 positivity in the tumor cells is a strong diagnostic clue. BRAF and KRAS mutations are rare in CNS RDD.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"366-375"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The predominance of \"astrocytic\" intranuclear inclusions in neuronal intranuclear inclusion disease manifesting encephalopathy-like symptoms: A case series with brain biopsy.","authors":"Keisuke Ishizawa, Takashi Komori, Taku Homma, Jun Sone, Yasuhiro Nakata, Yoshihiko Nakazato, Kazushi Takahashi, Toshimasa Yamamoto, Atsushi Sasaki","doi":"10.1111/neup.12971","DOIUrl":"10.1111/neup.12971","url":null,"abstract":"<p><p>Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder represented by eosinophilic intranuclear inclusions (EIIs) and GGC/CGG repeat expansion in the NOTCH2NLC gene. We report here two adult cases of NIID, genetically confirmed, with manifestation of encephalopathy-like symptoms and address the histopathologic findings obtained by brain biopsies, with a focus on \"astrocytic\" intranuclear inclusions (AIIs). Case 1 presented with paroxysmal restlessness, vertigo, or fever and was later involved in severe dementia and tetraparesis. Case 2 presented with forgetfulness and then with paroxysmal fever and headache. In both cases, delimited areas with gadolinium enhancement on magnetic resonance imaging and corresponding hyperperfusion were detected, leading to brain biopsies of the cortex. On histology, Case 1 showed an abnormal lamination, where the thickness of layers was different from usual. Both neurons and astrocytes showed some dysmorphologic features. Notably, astrocytes rather than neurons harbored EIIs. Case 2 showed a cortex, where neurons tended to be arrayed in a columnar fashion. Astrocytes showed some dysmorphologic features. Notably, much more astrocytes than neurons harbored EIIs. By a double-labeling immunofluorescence study for p62/NeuN and p62/glial fibrillary acidic protein, the predominance of AIIs was confirmed in both cases. Considering the physiological functions of astrocytes for the development and maintenance of the cortex, the encephalopathy-like symptoms, dynamic change of cerebral blood flow, and cortical dysmorphology can reasonably be explained by the dysfunction of EII-bearing astrocytes rather than EII-bearing neurons. This study suggests the presence of a subtype of NIID where AIIs rather than \"neuronal\" intranuclear inclusions are likely a key player in the pathogenesis of NIID, particularly in cases with encephalopathy-like symptoms. The importance of AIIs (\"gliopathy\") should be more appreciated in future studies of NIID.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"351-365"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemorrhage from metastatic brain epithelioid hemangioendothelioma: A case report.","authors":"Tatsuya Fusegawa, Takahiko Tomita, Noriko Okuno, Takuya Akai, Satoshi Kuroda","doi":"10.1111/neup.12969","DOIUrl":"10.1111/neup.12969","url":null,"abstract":"<p><p>In this report, we describe a very rare case of metastatic epithelioid hemangio-endothelioma (EHE) originating from other organs such as the lung and requiring craniotomy due to subsequent hemorrhage. A 50-year-old man was diagnosed with EHE in the bilateral lungs, the mediastinum, and the right adrenal gland 8 years earlier. One year earlier, he had developed spinal metastasis. Six months earlier, a screening brain MRI had revealed multiple brain metastases of tumor. He developed subcortical hemorrhage from the tumor in the right parietal lobe and successfully underwent removal of hematoma and tumor. Histopathological examinations revealed EHE. Metastatic EHE is very rare but may be at high risk of intracranial hemorrhage. It is quite important to consider the possibility of brain metastasis and subsequent bleeding when treating patients with EHE.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"338-343"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case of disseminated spinal astroblastoma harboring a MAMLD1::BEND2 fusion.","authors":"Erin N Walker, Maxwell T Laws, Francesca Cozzi, Martha Quezado, Desmond A Brown, Eric C Burton","doi":"10.1111/neup.12960","DOIUrl":"10.1111/neup.12960","url":null,"abstract":"<p><p>Astroblastoma, MN1-altered, is a rare neoplasm of the central nervous system (CNS). This malignancy shares similar histopathological features with other CNS tumors, including ependymomas, making it challenging to diagnose. DNA methylation profiling is a new and robust technique that may be used to overcome this diagnostic hurdle. We report the case of a now 25-year-old female diagnosed with what was initially called an ependymoma located in the cervical spine at the age of 2 years old. After initial resection, the tumor recurred multiple times and within 2 years of diagnosis had disseminated disease throughout the brain and spinal cord. She has now undergone over two decades of treatment, including multiple surgical resections, radiation therapy, and administration of numerous chemotherapeutic agents. In 2021, the patient presented to our institution with lumbosacral radicular symptoms due to enlarging lesions within the lumbosacral spine. Reexamination of formalin-fixed, paraffin-embedded material from the patient's tumor using genomic DNA methylation profiling resulted in a diagnostic change from grade III anaplastic ependymoma to astroblastoma, MN1-altered. This work describes another confirmed case of astroblastoma, MN1-altered, to the growing body of literature.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"278-284"},"PeriodicalIF":1.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11190029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticobasal degeneration with visual hallucination as an initial symptom: A case report.","authors":"Kentaro Yoshida, Tadashi Adachi, Yuki Suzuki, Mayuko Sakuwa, Hiroki Fukuda, Masato Hasegawa, Yoshiki Adachi, Hiroshi Miura, Ritsuko Hanajima","doi":"10.1111/neup.12963","DOIUrl":"10.1111/neup.12963","url":null,"abstract":"<p><p>Although the initial symptoms of corticobasal degeneration (CBD) are varied, psychiatric symptoms are uncommon. Here, we report the autopsy findings of a patient with early CBD who presented with hallucinations. A 68-year-old man developed memory loss and visions of bears and insects. Because of slow vertical eye movement, postural instability, and levodopa-unresponsive parkinsonism, the patient initially was clinically diagnosed with progressive supranuclear palsy. He died of a urinary tract infection 11 months after the onset of the disease. Histopathological examination revealed neuronal loss and gliosis, which were severe in the substantia nigra and moderate in the globus pallidus and subthalamic nucleus. Astrocytic plaques were scattered throughout the amygdala and premotor cortex. The superficial cortical layers lacked ballooned neurons and spongiosis, and tau deposition was greater in glia than in neurons. The amygdala contained a moderate number of argyrophilic grains and pretangles. Western blot analysis showed a 37-kDa band among the low-molecular-weight tau fragments. Because the CBD pathology was mild, we attributed the patient's visual hallucinations to the marked argyrophilic grain pathology. CBD can occur with psychiatric symptoms, including visual hallucinations, and argyrophilic grain pathology may be associated with psychiatric symptoms.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"298-303"},"PeriodicalIF":1.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An autopsy case of MV 2K + C subtype of Creutzfeldt-Jakob disease.","authors":"Akiko Uchino, Yuko Saito, Sho Tokuda, Yagishita Saburo, Shigeo Murayama, Kazuko Hasegawa","doi":"10.1111/neup.12964","DOIUrl":"10.1111/neup.12964","url":null,"abstract":"<p><p>Methionine/valine (MV) 2 type of sporadic Creutzfeldt-Jakob (sCJD) is divided into three subtypes based on neuropathological criteria: MV2-kuru (MV2K), MV2-cortical (MV2C), and MV2K + C, exhibiting the co-occurrence of these two pathological features. We report an autopsy case of MV2K + C subtype of sCJD. A 46-year-old Japanese man began to make mistakes at work. Two months later, he gradually developed gait instability. The initial neurological examination revealed limb ataxia and myoclonus. Diffusion-weighted images (DWI) showed a hyperintensity in the right frontal cortex, basal ganglia, and thalamus. Ten months after the onset of disease, he fell into akinetic mutism. He died at 47 years of age, 12 months after the initial presentation. Pathological investigation revealed microvacuolation and confluent vacuoles in the cerebral cortex. In the basal ganglia and thalamus, there was severe neuronal loss and gliosis with mild spongiform change. Kuru plaques were found within the cerebellum. Prion protein (PrP) immunostaining revealed synaptic, perivacuolar, perineuronal, and plaque-like deposits in the cerebral cortex. There were synaptic and plaque-like PrP deposits in the basal ganglia, thalamus, and granular cell layer of the cerebellum. In these areas, plaque-like deposits mainly consisted of small deposits, whereas plaque-like deposits in the cerebral cortex consisted both of coarse granular and small deposits. Analysis of the PrP gene showed no pathogenic mutations, and Western blot examination revealed a mixture of type 2 and intermediate-type PrP. The progressive cognitive decline and ataxia in addition to the hyperintensity in the basal ganglia and/or thalamus on DWI are the basis for clinical diagnosis of MV2. The severe gliosis in the basal ganglia and various morphologies of plaque-like deposits that differ by the region may be characteristic of MV2K + C. Detailed neuropathological examination together with Western blot analysis is important to collect more cases for elucidating the pathogenesis of MV2K + C.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"304-313"},"PeriodicalIF":1.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropilin-1 enhances temozolomide resistance in glioblastoma via the STAT1/p53/p21 axis.","authors":"Ping Huang, Lixia Zhang, Hongwei Wang, Changwu Dou, Haitao Ju, Peng Yue, Jiaxing Ren","doi":"10.1111/neup.12966","DOIUrl":"10.1111/neup.12966","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most prevalent primary intracranial tumor. Temozolomide (TMZ) is the first-line chemotherapy for GBM. Nonetheless, the development of TMZ resistance has become a main cause of treatment failure in GBM patients. Evidence suggests that neuropilin-1 (NRP-1) silencing can attenuate GBM cell resistance to TMZ. This study aims to determine potential mechanisms by which NRP-1 affects TMZ resistance in GBM. The parental U251 and LN229 GBM cells were exposed to increasing concentrations of TMZ to construct TMZ-resistant GBM cells (U251/TMZ, LN229/TMZ). BALB/c nude mice were injected with U251/TMZ cells to establish the xenograft mouse model. Functional experiments were carried out to examine NRP-1 functions. Western blotting and real-time quantitative polymerase chain reaction were used to evaluate molecular protein and mRNA expression, respectively. Immunohistochemical staining showed NRP-1 and STAT1 expression in mouse tumors. The results showed that NRP-1 was highly expressed in TMZ-resistant cells. Moreover, knocking down NRP-1 attenuated the TMZ resistance of U251/TMZ cells, while upregulating NRP-1 enhanced TMZ resistance of the parental cells. NRP-1 silencing elevated GBM cell sensitivity to TMZ in tumor-bearing mice. Depleting NRP-1 reduced STAT1, p53, and p21 expression in U251/TMZ cells. STAT1 depletion offset NRP-1 silencing evoked attenuation of GBM cell resistance to TMZ. Collectively, our study reveals that NRP-1 enhances TMZ resistance in GBM possibly by regulating the STAT1/p53/p21 axis.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"319-330"},"PeriodicalIF":1.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From pathological mechanisms in Krabbe disease to cutting-edge therapy: A comprehensive review.","authors":"Imen Ketata, Emna Ellouz","doi":"10.1111/neup.12967","DOIUrl":"10.1111/neup.12967","url":null,"abstract":"<p><p>Since its initial documentation by Knud Krabbe in 1916, numerous studies have scrutinized the characteristics of Krabbe disease (KD) until the identification of the mutation in the GALC gene. In alignment with that, we investigated the natural history of KD spanning eight decades to gain a deeper understanding of the evolutionary trajectory of its mechanisms. Through our comprehensive analysis, we unearthed additional novel elements in molecular biology involving the micropathological mechanism of the disease. This review offers an updated perspective on the metabolic disorder that defines KD. Recently, extracellular vesicles (EVs), autophagy impairment, and α-synuclein have emerged as pivotal players in the neuropathological processes. EVs might serve as a cellular mechanism to avoid or alleviate the detrimental impacts of excessive toxic psychosine levels, and extracting EVs could contribute to synapse dysfunction. Autophagy impairment was found to be independent of psychosine and reliant on AKT and B-cell lymphoma 2. Additionally, α-synuclein has been recognized for inducing cellular death and dysfunction in common biological pathways. Our objective is to assess the effectiveness of advanced therapies in addressing this particular condition. While hematopoietic stem cells have been a primary treatment, its administration proves challenging, particularly in the presymptomatic phase. In this review, we have compiled information from over 10 therapy trials, comparing them based on their benefits and disadvantage.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"255-277"},"PeriodicalIF":1.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}