Neuropathology and Applied Neurobiology最新文献

{"title":"A Case of Primary Intramedullary Infantile Fibrosarcoma With an RBPMS::NTRK3 Fusion and Response to Larotrectinib.","authors":"Mégane Le Quang, Julie Tandonnet, Nathalène Truffaux, Lucile Vanhersecke, Jean Delmas, Arthur Durouchoux, Dorian Bochaton, Arnault Tauziède-Espariat, Guillaume Chotard","doi":"10.1111/nan.70102","DOIUrl":"https://doi.org/10.1111/nan.70102","url":null,"abstract":"<p><p>We report a case of primary intramedullary infantile fibrosarcoma (IFS) in a 4-week-old infant with rapidly progressive cervical myelopathy. Histology showed a spindle cell tumour with diffuse S100 and pan-TRK expression. RNA sequencing identified an RBPMS::NTRK3 fusion. RNA-based clustering and DNA methylation profiling classified the tumour as IFS. Treatment with the TRK inhibitor, larotrectinib, achieved marked clinical and radiological recovery within 1 month, expanding the spectrum of NTRK-rearranged sarcomas and confirming TRK inhibition's efficacy in primary central nervous system IFS.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 5","pages":"e70102"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Rare Cause of Intraventricular Mass With Hydrocephalus in a Child: Central Nervous System Involvement of Hypereosinophilic Syndrome.","authors":"Yue Xi, Li Yuan, Dongzhi He, Xiaorui Zhao, Yuqing Cao, Mingjie Zhang, Huiying Wu","doi":"10.1111/nan.70103","DOIUrl":"https://doi.org/10.1111/nan.70103","url":null,"abstract":"<p><p>A child with hypereosinophilic syndrome presented with an intraventricular mass and hydrocephalus. Histopathology showed dense eosinophilic infiltration, supporting central nervous system involvement. This rare entity can mimic an intraventricular neoplasm and should be considered in the differential diagnosis.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 5","pages":"e70103"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Observations on a Low-Grade Diffusely Infiltrative Tumour, SMARCB1 Mutant, Arguing for a New Tumour Type.","authors":"Alice Métais, Giorgia Antonia Simboli, Marc Barritault, Fabrice Chrétien, Julien Masliah-Planchon, Alessandro Moiraghi, Johan Pallud, Laure Thomas, Pierre Leblond, Alexandre Bani-Sadr, Raphaël Saffroy, Arnault Tauziède-Espariat, Alexandre Vasiljevic, Pascale Varlet","doi":"10.1111/nan.70098","DOIUrl":"10.1111/nan.70098","url":null,"abstract":"<p><p>Two new cases of low-grade diffusely infiltrative tumour (LGDIT), SMARCB1 mutant, are described in an 18-year-old and a 50-year-old male, both with supratentorial lesions, characteristic rhabdoid histology on a myxoid-collagenous background, and complete INI1 loss. Both tumours showed homozygous SMARCB1 deletion and clustered with previously reported LGDIT on t-SNE analysis, in proximity to ATRT-MYC. These observations reinforce the distinct clinicopathological profile of LGDIT and support its consideration as a provisional CNS tumour type.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 5","pages":"e70098"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Papillary Tumour of the Pineal Region, in a Child With a Germline PTEN Pathogenic Variant, Arisen in the Fourth Ventricle.","authors":"Gianluca Marucci, Veronica Saletti, Rosina Paterra, Monica Patané, Cecilia Casali, Laura Grazia Valentini, Marco Moscatelli, Sara Bulgheroni, Alessandra Erbetta, Valeria Barresi","doi":"10.1111/nan.70093","DOIUrl":"10.1111/nan.70093","url":null,"abstract":"<p><p>We describe a unique case of papillary tumour of the pineal region (PTPR) arising in the fourth ventricle without any demonstrable anatomical continuity with the pineal region, in a 2-year-old male patient harbouring a germline PTEN pathogenic variant. This case arisen in the fourth ventricle shows epigenetic characteristics consistent with PTPR, suggesting the possibility that PTPR develops outside the pineal region. The tumour was composed of epithelioid-looking papillary structures (A, Haematoxylin and eosin [H&E]), intermingled with more densely cellular areas displaying perivascular pseudorosettes (B, H&E). Neoplastic cells resulted immunopositive for GFAP (C), CD56/NCAM (D) and focally positive for cytokeratin 18 (E) and showed dot-like immunostaining for EMA (F). DNA methylation profiling using the Bethesda Classifier version 2.0 demonstrated that the tumour clustered with PTPR-B in the UMAP analysis (G). CNV plot of the tumour showed the isolated loss of chromosome 10 (H).</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70093"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropathological Findings Following Failure of Laser Interstitial Thermal Therapy for an Epileptogenic Cerebral Cavernous Malformation.","authors":"Alberto Pietrantoni, Roberta Di Giacomo, Michele Rizzi, Valeria Cuccarini, Fabio Martino Doniselli, Rachele Colombo, Gianluca Marucci","doi":"10.1111/nan.70099","DOIUrl":"https://doi.org/10.1111/nan.70099","url":null,"abstract":"<p><p>We describe the case of a 32-year-old woman with focal drug-resistant epilepsy, who underwent surgical resection of a cerebral cavernous malformation (CCM), previously treated with laser interstitial thermal therapy (LITT), after experiencing seizure recurrence. Histological findings after LITT have been rarely described. We report and discuss neuropathological findings to explain post-LITT seizure recurrence, with a focus on extensive hemosiderin deposition and a minimal residue of the original CCM. This illustrative case may aid the comprehension of histological bases underlying the LITT failure in seizure relief.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70099"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transgenic A53T Mice Have Astrocytic α-Synuclein Aggregates in Dopamine and Striatal Regions.","authors":"Cormac Peat, Asheeta Prasad, David I Finkelstein, Caroline Sue, Jennifer A Johnston, Clare L Parish, Lachlan Thompson, Deniz Kirik, Glenda M Halliday","doi":"10.1111/nan.70097","DOIUrl":"https://doi.org/10.1111/nan.70097","url":null,"abstract":"<p><strong>Aims: </strong>The accumulation of α-synuclein in astrocytes in Parkinson's disease is considered to be secondary to neuronal accumulation. The aim of this study to identify whether astrocytes accumulate small α-synuclein aggregates before or after neurons in the nigrostriatal pathway.</p><p><strong>Methods: </strong>Fixed serial midbrain and striatal sections from M83 A53T transgenic mouse model of Parkinson's disease and wild-type controls were histologically processed for multiplex labelling of α-synuclein and astrocytic markers and astrocyte quantitation performed on digital images using QuPath software.</p><p><strong>Results: </strong>The density of astrocytes within the substantia nigra pars compacta was approximately 30% greater compared with other sampled regions (p < 0.005). Small aggregates of α-synuclein were observed in astrocytic processes, including in wild-type mice where a quarter of all astrocytes had an obvious α-synuclein aggregate. Compared to wild-type, A53T transgenic astrocytes had significantly enlarged somas (p < 0.001) with more processes (p < 0.001) consistent with a reactive phenotype. The A53T transgenic mice had more than double the numbers of astrocytes (p < 0.001) and 2.5 times more astrocytes with α-synuclein aggregates compared to wild-type mice (p < 0.001).</p><p><strong>Conclusions: </strong>These data suggest that small α-synuclein aggregates are normally cleared by astrocytes and that the substantia nigra pars compacta requires more astrocytic support for this function than other midbrain dopaminergic regions or the striatum. This adds another vulnerability factor to those already known for the substantia nigra with early deficits in clearance of small α-synuclein aggregates by astrocytes associated with increased astrocytic reactivity in the A53T transgenic mouse model.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70097"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13482139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontotemporal Lobar Degeneration-TDP Type C With Striatal Glial Cytoplasmic Inclusions and Motor Neuron Degeneration.","authors":"Akiko Uchino, Kazutomi Kanemaru, Airi Tarutani, Masato Hasegawa, Hiroya Naruse, Hiroyuki Ishiura, Shigeo Murayama, Yuko Saito","doi":"10.1111/nan.70090","DOIUrl":"10.1111/nan.70090","url":null,"abstract":"<p><p>We report an autopsy case of frontotemporal lobar degeneration (FTLD)-TDP type C with severe striatal involvement and annexin A11- and phosphorylated TDP-43-positive glial cytoplasmic inclusions. The patient developed progressive asymmetric rigidity accompanied by marked striatal atrophy and showed both upper and lower motor neuron involvement. These findings expand the clinicopathological spectrum of FTLD-TDP type C and may support the concept of an annexin A11-associated pathogenic continuum linking FTLD and amyotrophic lateral sclerosis.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70090"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central Nervous System Embryonal Tumour With PLAGL Amplification Lacking Typical Embryonal Morphology: Diagnostic Pitfall in a Paediatric Case.","authors":"Ryo Okuse, Sumihito Nobusawa, Akira Kurose, Akihisa Kamataki, Yuichi Sato, Ryo Sugimoto, Hiromichi Suzuki, Naoki Yanagawa, Takaaki Beppu","doi":"10.1111/nan.70087","DOIUrl":"10.1111/nan.70087","url":null,"abstract":"<p><p>Central nervous system embryonal tumour with PLAGL amplification, a methylation-defined tumour entity, may lack typical embryonal morphology. In this paediatric case, the diagnosis was established by DNA methylation profiling and confirmed by fluorescence in situ hybridisation demonstrating PLAGL1 amplification. Recognition of this morphology-molecular discordance may help avoid diagnostic pitfalls.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70087"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropathological and Molecular Features Associated With a Heterozygous DNAJC7 Mutation in Amyotrophic Lateral Sclerosis.","authors":"Yoshiaki Nakayama, Kodai Kume, Takashi Baba, Takashi Ayaki, Keisuke Hanada, Katsuichi Miyamoto, Norimitsu Inoue, Hideshi Kawakami, Hidefumi Ito","doi":"10.1111/nan.70086","DOIUrl":"10.1111/nan.70086","url":null,"abstract":"<p><strong>Aims: </strong>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with unclear molecular mechanisms. Heterozygous protein-truncating variants of DNAJC7, which encode a cochaperone involved in Hsp70/90-mediated protein quality control, are potential risk factors for ALS. However, the neuropathological consequences of heterozygous DNAJC7 mutations are unclear. We aimed to clarify the molecular and neuropathological features associated with a heterozygous DNAJC7 mutation in ALS.</p><p><strong>Methods: </strong>We genetically screened 39 Japanese patients with ALS and identified a novel heterozygous frameshift mutation in DNAJC7 (c.157_163del, p.Lys53Ter) in one patient that was neuropathologically diagnosed with Kii ALS. We performed biochemical and neuropathological analyses using postmortem tissues from this patient, from cases of ALS without the mutation and from control cases.</p><p><strong>Results: </strong>In the cases of ALS without DNAJC7 mutation, there was elevation of both DNAJC7 mRNA and protein levels compared with controls. The patient with DNAJC7 mutation showed relatively lower DNAJC7 mRNA and protein levels compared with the nonmutated cases of ALS, although mRNA expression remained relatively higher. DNAJC7 may be upregulated as a protective response against ALS pathogenesis, whereas a heterozygous mutation may attenuate this response. Immunohistochemistry and double immunofluorescence demonstrated partial colocalization of DNAJC7 with phospho-TDP-43-positive neuronal cytoplasmic inclusions, which supports a direct role for DNAJC7 in modulating pathological TDP-43 aggregation.</p><p><strong>Conclusions: </strong>These findings provide neuropathological evidence linking heterozygous DNAJC7 mutation to ALS, demonstrating impaired protein expression and suggesting a loss-of-function mechanism that compromises protective responses to TDP-43 pathology. DNAJC7 may represent a key modulator of ALS pathogenesis and potential therapeutic target.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70086"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of Optical Genome Mapping in the Characterisation of the Global Genomic Architecture of Paediatric Central Nervous System Tumours: A Pilot Study.","authors":"Viola Alesi, Silvia Genovese, Serena Russo, Isabella Giovannoni, Sabina Barresi, Chantal Tancredi, Lucia Pedace, Francesca Arienzo, Antonietta Lombardo, Piera Bontempo, Emanuele Agolini, Chiara Calacci, Alessandra Morgia, Giusy Calvieri, Chiara Puggioni, Antonello Cardoni, Antonella Cacchione, Giada Del Baldo, Giovanna Stefania Colafati, Andrea Carai, Angela Mastronuzzi, Evelina Miele, Damiano Abeni, Franco Locatelli, Andrea Onetti Muda, Antonio Novelli, Rita Alaggio, Sabrina Rossi","doi":"10.1111/nan.70092","DOIUrl":"10.1111/nan.70092","url":null,"abstract":"<p><strong>Introduction: </strong>Genomic instability is common in cancer, driven by different mechanisms and often linked to disease stage and progression. Optical genome mapping (OGM) enables the detection of genome-wide balanced and unbalanced structural rearrangements (SRs), providing an overview of genomic complexity.</p><p><strong>Aims: </strong>To explore the utility of OGM in brain tumour characterisation, we conducted a pilot study on a well-characterised series of 43, mostly paediatric, cases encompassing different histotypes and enriched for gene fusion-positive neoplasms (30 cases).</p><p><strong>Results: </strong>SRs were observed in 37/43 samples and defined three genomic patterns based on their number and distribution across the chromosomes: SR-chromothripsis (11 cases), high SR-complexity (11 cases) and low SR-complexity (21 cases). Genomic complexity was also assessed according to the number of copy number alterations (CNA) and, to this end, in SR-chromothripsis samples, only CNAs affecting chromosomes not involved in chromothripsis were considered: absence of CNAs was found in 15 cases, 1-9 CNAs in 19 cases, 10-49 CNAs in three cases and ≥ 50 CNAs in six cases. When examining the relationship between SR and CNA, a positive correlation emerged between CNA burden and the number of chromosomes harbouring SR (Spearman's r = 0.588, p = 0.0001), while breakpoint number was weakly associated; chromothripsis occurred exclusively within low CNA-complexity groups (p = 0.0836). Genome complexity patterns correlated with tumour types, with diffuse high-grade gliomas exhibiting high complexity, whereas infant-type hemispheric gliomas, most low-grade gliomas and embryonal tumours showed low complexity profiles. Importantly, SR-chromothripsis cases corresponded to low/intermediate-grade fusion-driven tumours, with balanced/nearly balanced CNA profiles. OGM allowed the detection of gene fusions in 24/30 cases, failing in six. When integrated with RNA sequencing, OGM unveiled the mechanisms underlying gene fusion formation in all cases: chromothripsis (11 cases), isolated chromosomal abnormalities (12 cases) and genome-wide alterations (seven cases).</p><p><strong>Conclusions: </strong>OGM reveals distinct genomic complexity patterns and refines the definition of chromothripsis, improving insights into tumourigenic mechanisms.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70092"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13364514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}