Brain Pathology最新文献

{"title":"The 2022 WHO classification of tumors of the pituitary gland: An update on aggressive and metastatic pituitary neuroendocrine tumors.","authors":"Olivera Casar-Borota, Pia Burman, M Beatriz Lopes","doi":"10.1111/bpa.13302","DOIUrl":"https://doi.org/10.1111/bpa.13302","url":null,"abstract":"<p><p>The vast majority of pituitary neuroendocrine tumors (PitNETs) are benign and slow growing with a low relapse rate over many years after surgical resection. However, about 40% are locally invasive and may not be surgically cured, and about one percentage demonstrate an aggressive clinical behavior. Exceptionally, these aggressive tumors may metastasize outside the sellar region to the central nervous system and/or systemically. The 2017 (4th Edition) WHO Classification of Pituitary Tumors abandoned the terminology \"atypical adenoma\" for tumors previously considered to have potential for a more aggressive behavior since its prognostic value was not established. The 2022 (5th Edition) WHO Classification of the Pituitary Tumors emphasizes the concept that morphological features distinguish indolent tumors from locally aggressive ones, however, the proposed histological subtypes are not consistent with the real life clinical characteristics of patients with aggressive tumors/carcinomas. So far, no single clinical, radiological or histological parameter can determine the risk of growth or malignant progression. Novel promising molecular prognostic markers, such as mutations in ATRX, TP53, SF3B1, and epigenetic DNA modifications, will need to be verified in larger tumor cohorts. In this review, we provide a critical analysis of the WHO guidelines for prognostic stratification and diagnosis of aggressive and metastatic PitNETs. In addition, we discuss the new WHO recommendations for changing ICD-O and ICD-11 codes for PitNET tumor behavior from a neoplasm either \"benign\" or \"unspecified, borderline, or uncertain behavior\" to \"malignant\" neoplasm regardless of the clinical presentation, histopathological subtype, and tumor location. We encourage multidisciplinary initiatives for integrated clinical, histological and molecular classification, which would enable early recognition of these challenging tumors and initiation of more appropriate and aggressive treatments, ultimately improving the outcome.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13302"},"PeriodicalIF":5.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104591","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":"Grading and staging for pituitary neuroendocrine tumors.","authors":"Chiara Villa, Maria Francesca Birtolo, Perez-Rivas Luis Gustavo, Alberto Righi, Guillaume Assie, Bertrand Baussart, Sofia Asioli","doi":"10.1111/bpa.13299","DOIUrl":"10.1111/bpa.13299","url":null,"abstract":"<p><p>Pituitary adenoma/pituitary neuroendocrine tumors (PitNETs) are the second most common primary intracranial tumor and the most frequent neuroendocrine tumors/neoplasms of the human body. Thus, they are one of the most frequent diagnoses in neuropathologist's practise. 2022 5th edition WHO Classification of Endocrine and Neuroendocrine Tumors does not support a grading and/or staging system for PitNETs and argues that histological typing and subtyping are more robust than proliferation rate and invasiveness to stratify tumors. Numerous studies suggest the existence of clinically relevant molecular subgroups encouraging an integrated histo-molecular approach to the diagnosis of PitNETs to deepen the understanding of their biology and overcome the unresolved problem of grading system. The present review illustrates the main issues involved in establishing a grading and a staging system, as well as alternative systems validated by independent series to date. The state of art of the current histological and molecular markers is detailed, demonstrating that a standardized and reproducible clinico-pathological approach, combined with the integration of molecular data may help build a workflow to refine the definition of PitNETs with 'malignant potential' and most importantly, avoid delay in patient treatment. Next molecular studied are needed to validate an integrated histo-molecular grading for PitNETs.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13299"},"PeriodicalIF":5.8,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054966","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":"Practical approaches to diagnosing PitNETs/adenomas based on cell lineage.","authors":"Abhijit Goyal-Honavar, Geeta Chacko","doi":"10.1111/bpa.13298","DOIUrl":"https://doi.org/10.1111/bpa.13298","url":null,"abstract":"<p><p>The evolution of classification systems of pituitary adenomas (now PitNETs) has culminated in the use of transcription factor (TF) immunohistochemistry (IHC), forming a cell lineage-based system. However, several issues remain to be addressed, including the additional financial and logistic burden of undertaking the complete array of anterior pituitary hormones and TF IHC. To that end, several groups have suggested algorithms to minimise the number of tests performed, with varying levels of diagnostic accuracy. Although the proportion of null cell tumours has decreased following the use of TFs, \"multilineage\" tumours have been reported and characterised using transcriptomic signatures, most prominently the PIT1-SF1 co-expressing PitNETs, which do not bear a position in the present system of classification. In this review, we examine the proposed practical approaches to the diagnosis of PitNETs. We review the literature on reported PitNET types that challenge the existing classification system, such as those that express multiple TFs, with their potential clinical implications. Finally, we assess limitations in the present system, such as the lack of a standardised system for IHC interpretation, that need to be addressed in the future.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13298"},"PeriodicalIF":5.8,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054967","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":"Deep learning-based segmentation in MRI-(immuno)histological examination of myelin and axonal damage in normal-appearing white matter and white matter hyperintensities.","authors":"Gemma Solé-Guardia, Matthijs Luijten, Esther Janssen, Ruben Visch, Bram Geenen, Benno Küsters, Jurgen A H R Claassen, Geert Litjens, Frank-Erik de Leeuw, Maximilian Wiesmann, Amanda J Kiliaan","doi":"10.1111/bpa.13301","DOIUrl":"https://doi.org/10.1111/bpa.13301","url":null,"abstract":"<p><p>The major vascular cause of dementia is cerebral small vessel disease (SVD). Its diagnosis relies on imaging hallmarks, such as white matter hyperintensities (WMH). WMH present a heterogenous pathology, including myelin and axonal loss. Yet, these might be only the \"tip of the iceberg.\" Imaging modalities imply that microstructural alterations underlie still normal-appearing white matter (NAWM), preceding the conversion to WMH. Unfortunately, direct pathological characterization of these microstructural alterations affecting myelinated axonal fibers in WMH, and especially NAWM, is still missing. Given that there are no treatments to significantly reduce WMH progression, it is important to extend our knowledge on pathological processes that might already be occurring within NAWM. Staining of myelin with Luxol Fast Blue, while valuable, fails to assess subtle alterations in white matter microstructure. Therefore, we aimed to quantify myelin surrounding axonal fibers and axonal- and microstructural damage in detail by combining (immuno)histochemistry with polarized light imaging (PLI). To study the extent (of early) microstructural damage from periventricular NAWM to the center of WMH, we refined current analysis techniques by using deep learning to define smaller segments of white matter, capturing increasing fluid-attenuated inversion recovery signal. Integration of (immuno)histochemistry and PLI with post-mortem imaging of the brains of individuals with hypertension and normotensive controls enables voxel-wise assessment of the pathology throughout periventricular WMH and NAWM. Myelin loss, axonal integrity, and white matter microstructural damage are not limited to WMH but already occur within NAWM. Notably, we found that axonal damage is higher in individuals with hypertension, particularly in NAWM. These findings highlight the added value of advanced segmentation techniques to visualize subtle changes occurring already in NAWM preceding WMH. By using quantitative MRI and advanced diffusion MRI, future studies may elucidate these very early mechanisms leading to neurodegeneration, which ultimately contribute to the conversion of NAWM to WMH.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13301"},"PeriodicalIF":5.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035315","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":"Society News","authors":"","doi":"10.1111/bpa.13292","DOIUrl":"https://doi.org/10.1111/bpa.13292","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994289","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":"Multiple intra-axial lesions in a 57-year-old male with a history of B-cell chronic lymphocytic leukemia","authors":"Sofia Asioli,&nbsp;Lina Cardisciani,&nbsp;Matteo Martinoni,&nbsp;Caterina Tonon,&nbsp;Rocco Liguori,&nbsp;Pierluigi Zinzani,&nbsp;Luisa Di Sciascio,&nbsp;Elena Sabattini","doi":"10.1111/bpa.13296","DOIUrl":"10.1111/bpa.13296","url":null,"abstract":"&lt;p&gt;A 57-year-old male with a recent history of B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (BCLL/SLL), developed a persistent left-frontal headache. One month after the onset of headache and 2 days after the second dose of anti-SARS-CoV2 mRNA vaccine, he developed a persistent high fever. He was monitored for the following days and 20 days later, he experienced tonic–clonic seizures with post-critical coma (Day 1). CT and MRI scans showed multiple sub and supra-tentorial intra-axial edematous lesions with contrast enhancement and without mass effect, as shown in Figure 1. He started dexamethasone and levetiracetam with subsequent total recovery of vigilance on Day 3 (Box 1).&lt;/p&gt;&lt;p&gt;On Day 6, a stereotactic biopsy of the major frontal lesion showed the presence of necrotic tissue. Following clinical improvement, on Day 9 he was discharged, with dexamethasone taping from Day 20. On Day 40 a control RMI showed edema reduction, but new nodules appeared. He was admitted again and underwent CSF analysis, lymphocyte characterization, blood culture, and total body &lt;sup&gt;18&lt;/sup&gt;FDG-PET-CT, all non-contributive.&lt;/p&gt;&lt;p&gt;Still, under steroid tapering, the patient became unresponsive and febrile again, so corticosteroid dosing was increased. After initial improvement he went into hyponatremic coma, consistent with inappropriate ADH secretion syndrome. A new MRI showed a further increase in the lesions and expanded edema. On Day 67 a new open biopsy of the left frontal lesion was performed. After histologic diagnosis, the patient was referred to the Onco-Hematology department where a bone marrow biopsy confirmed a modest infiltration by BCLL/SLL (10% of cellularity). Chemotherapy with MATRix regimen was started with only mild improvement. He ultimately succumbed to the disease on Day 98.&lt;/p&gt;&lt;p&gt;On hematoxylin–eosin the lesion showed extensive necrosis with predominantly medium-sized, atypical lymphoid cells with irregular nuclei, moderate amount of pale cytoplasm with vascular proliferation and histiocytic elements (Figure 2A–C). The neoplastic cells displayed angiocentric growth, mitoses, and apoptotic bodies. CD3 (Figure 2D) and CD2 were positive in neoplastic cells (Figure 2E) as well as Beta-F1 for the αβ T-cell receptor (TCR) dimer; CD20, PAX5, CD5, CD7, CD4, CD8, TdT, CD56, Tia-1, and TCR-γ dimer were negative. Epstein–Barr virus-encoded small RNAs were not detected at in situ hybridization. TCR Gamma rearrangement (TRG) was analyzed by GeneScanning and two distinct reproducible peaks were detected (Figure 2E) interpreted as either a biallelic or biclonal rearrangement.&lt;/p&gt;&lt;p&gt;Peripheral T cell lymphoma, Not Otherwise Specified (NOS) consistent with Primary CNS T cell lymphoma.&lt;/p&gt;&lt;p&gt;Peripheral T-cell lymphoma (PTCLs) accounts for 2%–4% of primary CNS lymphomas in Europe. Immunodeficiency might play a role in the etiology of the disease in a subset of patients. Involved sites include the frontal and temporal lobes, cerebellum, pituitary, a","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900937","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":"Microtubule-associated NAV3 regulates invasive phenotypes in glioblastoma cells.","authors":"Aneta Škarková, Markéta Pelantová, Ondřej Tolde, Anna Legátová, Rosana Mateu, Petr Bušek, Elena Garcia-Borja, Aleksi Šedo, Sandrine Etienne-Manneville, Daniel Rösel, Jan Brábek","doi":"10.1111/bpa.13294","DOIUrl":"https://doi.org/10.1111/bpa.13294","url":null,"abstract":"<p><p>Glioblastomas are aggressive brain tumors for which effective therapy is still lacking, resulting in dismal survival rates. These tumors display significant phenotypic plasticity, harboring diverse cell populations ranging from tumor core cells to dispersed, highly invasive cells. Neuron navigator 3 (NAV3), a microtubule-associated protein affecting microtubule growth and dynamics, is downregulated in various cancers, including glioblastoma, and has thus been considered a tumor suppressor. In this study, we challenge this designation and unveil distinct expression patterns of NAV3 across different invasion phenotypes. Using glioblastoma cell lines and patient-derived glioma stem-like cell cultures, we disclose an upregulation of NAV3 in invading glioblastoma cells, contrasting with its lower expression in cells residing in tumor spheroid cores. Furthermore, we establish an association between low and high NAV3 expression and the amoeboid and mesenchymal invasive phenotype, respectively, and demonstrate that overexpression of NAV3 directly stimulates glioblastoma invasive behavior in both 2D and 3D environments. Consistently, we observed increased NAV3 expression in cells migrating along blood vessels in mouse xenografts. Overall, our results shed light on the role of NAV3 in glioblastoma invasion, providing insights into this lethal aspect of glioblastoma behavior.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13294"},"PeriodicalIF":5.8,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888534","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":"A pituitary mass in a 46-year-old woman","authors":"Francesco E. Emiliani,&nbsp;Donald C. Green,&nbsp;Edward G. Hughes,&nbsp;Wahab A. Khan,&nbsp;George J. Zanazzi,&nbsp;Chun-Chieh Lin","doi":"10.1111/bpa.13295","DOIUrl":"10.1111/bpa.13295","url":null,"abstract":"&lt;p&gt;A 46-year-old woman presented to the clinic with a 6-week history of left retro-orbital headaches. In recent weeks, she had developed increased thirst, a salty taste, and diplopia with blurry vision in the left eye. On examination, left cranial nerve six palsy was noted. Magnetic resonance imaging (MRI) revealed a 2.7 cm heterogeneously enhancing pituitary mass (Figure 1). Laboratory findings showed slightly elevated prolactin (83.8 ng/mL; reference: 4.8–23.3 ng/mL). There were no other findings associated with hypo/hyperpituitarism. During transsphenoidal resection, the tumor appeared to be adherent and firm with indistinct boundary with the pituitary gland. A portion of the tumor infiltrating the cavernous sinus was left behind to prevent damage to the cavernous segment of the carotid artery.&lt;/p&gt;&lt;p&gt;Intraoperative cytological smears showed pleomorphic tumor cells with prominent nucleoli and minimal cytoplasm (Figure 2A and Box 1). Histological examination of formalin-fixed paraffin-embedded (FFPE) tissue showed a poorly differentiated neoplasm with high mitotic counts (up to five per high-power field), forming a sheet-like architecture. Tumor cells exhibited prominent nucleoli and vesicular chromatin with cytoplasmic vacuolation. Occasional intracytoplasmic globular eosinophilic inclusions were noted (Figure 2B). Immunohistochemical study showed that the tumor was negative for CK (AE1/AE3), GFAP, synaptophysin, LCA, Melan A, HMB-45, Oct3/4, PLAP, and brachyury. Notably, the tumor showed loss of nuclear SMARCB1/INI1 staining (Figure 2C). Ki67 index was elevated (70%).&lt;/p&gt;&lt;p&gt;Chromosomal microarray analysis (CMA) demonstrated copy neutral loss of heterozygosity (cnLOH) in nearly the entire chromosome 22 that includes the &lt;i&gt;SMARCB1&lt;/i&gt; locus at 22q11.2 (Figure 2D). Next-generation sequencing (NGS) detected a frameshift deletion in the 3′ end of &lt;i&gt;SMARCB1&lt;/i&gt; (p. P383Rfs c.1148del; VAF = 74.2%) (Figure 2E). No other mutation was identified. Brain tumor methylation profiling from National Cancer Institute classified this tumor as an AT/RT subclass MYC (calibrated score of 0.95).&lt;/p&gt;&lt;p&gt;Adult sellar atypical teratoid/rhabdoid tumor, CNS WHO grade 4.&lt;/p&gt;&lt;p&gt;Adult sellar AT/RT is a rare, aggressive CNS embryonal tumor, with less than 50 cases reported to date. By definition, it occurs in the sellar/suprasellar region of adults, displays variable polyphenotypic differentiation and demonstrates characteristic &lt;i&gt;SMARCB1&lt;/i&gt; mutations. Notably, there is a strong female predominance (95%) and middle age distribution (mean = 44 ± 3 years) [&lt;span&gt;1-3&lt;/span&gt; and current case]. This contrasts with pediatric AT/RT, which shows a slight male predominance and has not been reported in the sellar region.&lt;/p&gt;&lt;p&gt;On MRI, adult sellar AT/RT is frequently described as a heterogeneously enhancing pituitary mass with invasion of adjacent structures. Due to its rarity and non-specific histological findings, the differential diagnosis is usually broad [&lt;span&gt;1-3&lt;/span&gt;]. A","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874212","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":"Transmembrane and coiled-coil 2 associates with Alzheimer's disease pathology in the human brain.","authors":"Paul C R Hopkins, Claire Troakes, Andrew King, Guy Tear","doi":"10.1111/bpa.13290","DOIUrl":"https://doi.org/10.1111/bpa.13290","url":null,"abstract":"<p><p>Transmembrane and coiled-coil 2 (TMCC2) is a human orthologue of the Drosophila gene dementin, mutant alleles of which cause neurodegeneration with features of Alzheimer's disease (AD). TMCC2 and Dementin further have an evolutionarily conserved interaction with the amyloid protein precursor (APP), a protein central to AD pathogenesis. To investigate if human TMCC2 might also participate in mechanisms of neurodegeneration, we examined TMCC2 expression in late onset AD human brain and age-matched controls, familial AD cases bearing a mutation in APP Val717, and Down syndrome AD. Consistent with previous observations of complex formation between TMCC2 and APP in the rat brain, the dual immunocytochemistry of control human temporal cortex showed highly similar distributions of TMCC2 and APP. In late onset AD cases stratified by APOE genotype, TMCC2 immunoreactivity was associated with dense core senile plaques and adjacent neuronal dystrophies, but not with Aβ surrounding the core, diffuse Aβ plaques or tauopathy. In Down syndrome AD, we observed in addition TMCC2-immunoreactive and methoxy-X04-positive pathological features that were morphologically distinct from those seen in the late onset and familial AD cases, suggesting enhanced pathological alteration of TMCC2 in Down syndrome AD. At the protein level, western blots of human brain extracts revealed that human brain-derived TMCC2 exists as at least three isoforms, the relative abundance of which varied between the temporal gyrus and cerebellum and was influenced by APOE and/or dementia status. Our findings thus implicate human TMCC2 in AD via its interactions with APP, its association with dense core plaques, as well as its alteration in Down syndrome AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13290"},"PeriodicalIF":5.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859071","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":"The historical background of hereditary cystatin C amyloid angiopathy: Genealogical, pathological, and clinical manifestations.","authors":"Asbjorg Osk Snorradottir, Hakon Hakonarson, Astridur Palsdottir","doi":"10.1111/bpa.13291","DOIUrl":"https://doi.org/10.1111/bpa.13291","url":null,"abstract":"<p><p>Hereditary cystatin C amyloid angiopathy (HCCAA) is an Icelandic disease that belongs to a disease class called cerebral amyloid angiopathy, a group of heterogenous diseases presenting with aggregation of amyloid complexes and deposition predominantly in the central nervous system. HCCAA is dominantly inherited, caused by L68Q mutation in the cystatin C gene, leading to aggregation of the cystatin C protein. HCCAA is a very progressive and severe disease, with widespread cerebral and parenchymal cystatin C and collagen IV deposition within the central nervous system (CNS) but also in other organs in the body, for example, in the skin. Most L68Q carriers have clinical symptoms characterized by recurrent hemorrhages and dementia, between the age of 20-30 years. If the carriers survive the first hemorrhage, the frequency and severity of the hemorrhages tend to increase, resulting in death at average of 30 years with mean number of major hemorrhages ranging from 3.2 to 3.9 over a 5-year average life span. The pathogenesis of the disease in carriers is very similar in the CNS and in the skin based on autopsy studies, thus skin biopsies can be used to monitor the progression of the disease by quantifying the cystatin C immunoreactivity. The cystatin C deposition always colocalizes with collagen IV and fibroblasts in the skin are found to be the main cell type responsible for the deposition of both proteins. No therapy is available for this devastating disease.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13291"},"PeriodicalIF":5.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757234","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}