Neuropathology最新文献

{"title":"Supratentorial multifocal gliomas associated with Ollier disease harboring IDH1 R132H mutation: A case report.","authors":"Hiroshi Ikeda,&nbsp;Shigeru Yamaguchi,&nbsp;Yukitomo Ishi,&nbsp;Kento Wakabayashi,&nbsp;Ai Shimizu,&nbsp;Hiromi Kanno-Okada,&nbsp;Takeshi Endo,&nbsp;Mitsutoshi Ota,&nbsp;Michinari Okamoto,&nbsp;Hiroaki Motegi,&nbsp;Norimasa Iwasaki,&nbsp;Miki Fujimura","doi":"10.1111/neup.12902","DOIUrl":"10.1111/neup.12902","url":null,"abstract":"<p><p>Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"413-420"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9141130","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 progressive multifocal leukoencephalopathy with massive iron deposition in juxtacortical lesions.","authors":"Kosuke Okamoto,&nbsp;Akitoshi Takeda,&nbsp;Hiroyuki Hatsuta,&nbsp;Terunori Sano,&nbsp;Masaki Takao,&nbsp;Masahiko Ohsawa,&nbsp;Yukio Miki,&nbsp;Kazuo Nakamichi,&nbsp;Yoshiaki Itoh","doi":"10.1111/neup.12898","DOIUrl":"10.1111/neup.12898","url":null,"abstract":"<p><p>Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by JC virus infection of oligodendrocytes. Little has been reported on iron deposits in patients with PML. Herein, we report a case of PML with massive iron deposition in the juxtacortical regions attaching white matter lesions in a 71-year-old woman who developed bilateral visual disturbance and progressive aphasia after 16 months of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone treatment for follicular lymphoma. Magnetic resonance imaging revealed white matter lesions in the left parietal and other lobes with massive iron deposition in the juxtacortical lesions. A PCR test for JC virus was positive, confirming the diagnosis of PML. Despite treatment with mefloquine and mirtazapine, the patient died six months later. At autopsy, demyelination was found dominantly in the left parietal lobe. Moreover, hemosiderin-laden macrophages and reactive astrocytes containing ferritin were abundant in the juxtacortical regions adjacent to the white matter lesions. This is a previously unreported case of PML after lymphoma, in which iron deposition was confirmed both radiologically and pathologically.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"396-402"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10837986","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":"Lymphomatosis cerebri with coexistent anti-N-methyl-D-aspartate receptor antibody: A case report.","authors":"Natthapon Rattanathamsakul,&nbsp;Tatchaporn Ongphichetmetha,&nbsp;Pattharasaya Weerachotisakul,&nbsp;Nanthaya Tisavipat,&nbsp;Pornsuk Cheunsuchon,&nbsp;Jiraporn Jitprapaikulsan","doi":"10.1111/neup.12899","DOIUrl":"10.1111/neup.12899","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"403-407"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10763977","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":"Pilocytic astrocytoma harboring a novel GNAI3-BRAF fusion.","authors":"Ruihe Lin,&nbsp;Alicia Kenyon,&nbsp;Zi-Xuan Wang,&nbsp;Jingli Cai,&nbsp;Lorraine Iacovitti,&nbsp;Lawrence C Kenyon","doi":"10.1111/neup.12896","DOIUrl":"10.1111/neup.12896","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"391-395"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10715899","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 \"genetically defined\" radiation-induced glioma: 29 years after surgery and radiation for pilocytic astrocytoma.","authors":"Kenta Masui,&nbsp;Masayuki Nitta,&nbsp;Yoshihiro Muragaki,&nbsp;Takakazu Kawamata,&nbsp;Kaishi Satomi,&nbsp;Yuko Matsushita,&nbsp;Akihiko Yoshida,&nbsp;Koichi Ichimura,&nbsp;Masumi Tsuda,&nbsp;Shinya Tanaka,&nbsp;Takashi Komori","doi":"10.1111/neup.12903","DOIUrl":"10.1111/neup.12903","url":null,"abstract":"Radiation-induced gliomas (RIGs), which occur in a previously irradiated region of the original tumor, represent a rare but well-characterized clinical entity. They are particularly represented as secondary malignancies after irradiation for medulloblastoma (MB) and acute lymphoblastic leukemia (ALL). Clinically well recognized, their genetic characteristics have remained unclear, but recent molecular studies revealed their unifying molecular signature for the receptor tyrosine kinase 1 (RTK1) glioblastoma (GBM) subtype. We present a case of RIG that emerged 29 years after surgery and radiation for pilocytic astrocytoma (PA); the distinctive molecular features of RIGs enabled its differentiation from malignant transformation of PA. All methods and protocols related to human subjects were approved by each institution’s review board ethics committee, and the investigations were carried out in accordance with each institution’s review board-approved protocol and Declaration of Helsinki of 2013. A 33-year-old woman had a history of subtotal resection of the right temporal lobe tumor at age 3. The histopathological diagnosis of the tumor was PA, and local radiation was performed for the residual lesion with parallel opposing fields of linear accelerator (LINAC), including right temporal and frontal lobes. She presented with nausea and headache 29 years later after radiation therapy, and magnetic resonance imaging (MRI) revealed an approximately 4-cm mass with ring enhancement within the irradiated region of the right frontal lobe (Fig. 1A). The patient underwent total resection of the tumor. Histologically, the tumor showed fascicular streaming of short-spindle, astrocytic tumor cells (Fig. 1B). They displayed immunoreactivity for glial markers, including glial fibrillary acidic protein (GFAP) (mouse monoclonal, clone 6F2; Dako, Glostrup, Denmark; 1:1000) and OLIG2 (rabbit polyclonal; IBL, Gunma, Japan; 1:200). The presence of palisading necrosis and microvascular proliferation suggested high-grade astrocytic tumors, including GBM induced by radiation (Fig. 1B). Molecular testing was performed by immunohistochemistry, reverse transcription-polymerase chain reaction (RTPCR), Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and 850 K methylation array (Infinium Methylation EPIC, Illumina), using samples from formalin-fixed paraffin-embedded (FFPE) or snap-frozen tissue. The tumor was negative for IDH1 p.R132H (mouse monoclonal, clone DIA-H09; Dianova, Hamburg, Germany; 1:500) and p53 (mouse monoclonal, clone DO-7; Nichirei Biosciences, Tokyo, Japan; pre-diluted), and alpha thalassemia/mental retardation syndrome X-linked (ATRX) (rabbit monoclonal, clone E5X7O; Cell Signaling, Danvers, MA; 1:1000) immunoreactivity was lost (Fig. 1B). Ki-67-positive ratio (mouse monoclonal, clone MIB-1; Dako; 1:500) was 20% (Fig. 1B), and MGMT promoter was unmethylated. KIAA1549::BRAF fusion was not detected by RT-PCR (Fig. S1B). Direct sequenci","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"425-428"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9169823","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":"Astrocytoma (CNS WHO grade 4), IDH-mutant with co-occurrence of BRAF p.V600E mutation, and homozygous loss of CDKN2A.","authors":"Henning Leske,&nbsp;Hanne Blakstad,&nbsp;Marius Lund-Iversen,&nbsp;Else Kathrine Skovholt,&nbsp;Pitt Niehusmann,&nbsp;Jon-Terje Ramm-Pettersen,&nbsp;Karoline Skogen,&nbsp;Geir Kongelf,&nbsp;Mette Sprauten,&nbsp;Henriette Magelssen,&nbsp;Petter Brandal","doi":"10.1111/neup.12895","DOIUrl":"10.1111/neup.12895","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"385-390"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10672685","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":"Expanded ischemic lesion due to herniation leads to axonal injury in a site remote to the primary lesion on autopsy brain with acute focal cerebral ischemia.","authors":"Erika Seki,&nbsp;Takashi Komori,&nbsp;Nobutaka Arai","doi":"10.1111/neup.12900","DOIUrl":"10.1111/neup.12900","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"373-384"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10807348","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":"Low-grade B-cell lymphoma of the central nervous system with plasmacytic differentiation and amyloid deposition.","authors":"Gianluca Lopez,&nbsp;Karam Han,&nbsp;Shino D Magaki,&nbsp;Sophie X Song,&nbsp;Noriko Salamon,&nbsp;Kanwarpal S Kahlon,&nbsp;Inna Keselman,&nbsp;Ausaf A Bari,&nbsp;Harry V Vinters","doi":"10.1111/neup.12886","DOIUrl":"https://doi.org/10.1111/neup.12886","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"43 4","pages":"313-318"},"PeriodicalIF":2.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9922093","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":"Midline brain hamartomatous lesions in fibrodysplasia ossificans progressiva with ACVR1 mutations.","authors":"Jesse Lee Kresak,&nbsp;Meggen Walsh,&nbsp;Anthony Tuzzolo,&nbsp;Zehra Ordulu,&nbsp;Jason Gregory","doi":"10.1111/neup.12892","DOIUrl":"https://doi.org/10.1111/neup.12892","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"43 4","pages":"333-339"},"PeriodicalIF":2.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9919285","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":"Pediatric and elderly polymorphous low-grade neuroepithelial tumor of the young: Typical and unusual case reports and literature review.","authors":"Takuya Furuta,&nbsp;Mayuko Moritsubo,&nbsp;Hiroko Muta,&nbsp;Hotetsu Shimamoto,&nbsp;Koichi Ohshima,&nbsp;Yasuo Sugita","doi":"10.1111/neup.12889","DOIUrl":"https://doi.org/10.1111/neup.12889","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"43 4","pages":"319-325"},"PeriodicalIF":2.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9976391","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}