NeuropathologyPub Date : 2026-08-01DOI: 10.1111/neup.70073
Shunsuke Koga, Ilya M Nasrallah, Rachel Blue, Juan Pablo Ospina, Steven Brem, Jason Shpilsky, MacLean Nasrallah, Zissimos Mourelatos
{"title":"Metachronous Pineal Germinoma 11 Years After Total Resection of a Mature Teratoma.","authors":"Shunsuke Koga, Ilya M Nasrallah, Rachel Blue, Juan Pablo Ospina, Steven Brem, Jason Shpilsky, MacLean Nasrallah, Zissimos Mourelatos","doi":"10.1111/neup.70073","DOIUrl":"10.1111/neup.70073","url":null,"abstract":"<p><p>Central nervous system germ cell tumors are uncommon and include germinomas, teratomas, and other nongerminomatous germ cell tumors. Mature teratomas are usually cured by complete resection, but rare patients later develop a histologically distinct malignant germ cell tumor. We report a man who presented at age 20 years with a cystic pineal lesion. Gross-total resection at age 21 years showed a mature teratoma with bronchogenic differentiation and no overt immature or malignant component on H&E. Serial postoperative MRI for 3 years showed no recurrence. Eleven years after surgery, he developed headache, gait disturbance, and confusion due to a 4.6-cm pineal mass with obstructive hydrocephalus. Serum alpha-fetoprotein was normal, whereas beta-human chorionic gonadotropin (β-hCG) was elevated. The resected tumor showed sheets of large round cells with clear cytoplasm and dense lymphocytes. Immunohistochemistry demonstrated strong nuclear OCT4 and SALL4 and membranous c-KIT, with focal β-hCG-positive syncytiotrophoblastic giant cells. No nongerminomatous germ cell tumor component was identified, supporting a diagnosis of germinoma with focal syncytiotrophoblastic giant cells. After this diagnosis, retrospective evaluation of the initial tumor showed multifocal, patchy OCT4 immunoreactivity in scattered cells along the ciliated respiratory-type epithelial lining. SALL4, c-KIT, and PLAP were focally positive in corresponding regions. These findings raised the possibility of an occult germ cell marker-positive population, although no discrete expansile germinoma component was identified. This case illustrates that metachronous germinoma can develop after a long disease-free interval following resection of a mature teratoma and highlights the value of retrospective pathologic evaluation and long-term surveillance.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 4","pages":"e70073"},"PeriodicalIF":1.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689443","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":"CD163 Dominance Within Macrophages/Microglia Reflects a Favorable Prognosis in Patients With Glioblastoma.","authors":"Mayuko Moritsubo, Takuya Furuta, Aya Hashimoto, Hidenobu Yoshitake, Tetsuya Negoto, Hideo Nakamura, Motohiro Morioka, Hiroaki Miyoshi","doi":"10.1111/neup.70071","DOIUrl":"10.1111/neup.70071","url":null,"abstract":"<p><p>Glioblastoma is the most common primary malignant central nervous system (CNS) tumor; however, its microenvironment, including tumor-associated microglia/macrophages (TAMs), is not fully understood. Although ionized calcium-binding adaptor molecule 1 (IBA-1) is expressed in various microglial phenotypes in the healthy human brain, CD163 is a marker of activated/phagocytic microglia. Tissues from 34 patients with glioblastoma were analyzed, and 17.6% of cases were CD163-dominant. CD163-dominant patients showed better overall survival than IBA-1-dominant patients (p = 0.019). CD163 dominance was identified as an independent prognostic factor for overall survival (hazard ratio [HR], 0.17; p = 0.011). Compared with the IBA-1-dominant group, CD163-dominant tumors showed more CD4-positive cell infiltration (p = 0.005), fewer ameboid TAMs (p = 0.021), and fewer non-microvascular proliferation (non-MVP) vessels (p = 0.012). No significant differences were found in patient characteristics, such as age, sex, tumor location, or extent of resection. The CD163-to-IBA-1 ratio of TAMs is a significant independent prognostic factor in glioblastoma, suggesting that the activation status of these cells and their interactions with the vascular endothelium and T cells influence tumor progression. These findings highlight TAMs as potential therapeutic targets for glioblastoma.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 4","pages":"e70071"},"PeriodicalIF":1.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471835","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}
NeuropathologyPub Date : 2026-08-01DOI: 10.1111/neup.70070
Rama Aburass, Sarah Al Sharie, Nisreen Amaiyri, Nasim Sarhan, Mouness Obeidat, Maysa Al-Hussaini
{"title":"Primary Intracranial CIC-Rearranged Sarcoma With Prior History of B-Cell ALL: A Case Report.","authors":"Rama Aburass, Sarah Al Sharie, Nisreen Amaiyri, Nasim Sarhan, Mouness Obeidat, Maysa Al-Hussaini","doi":"10.1111/neup.70070","DOIUrl":"10.1111/neup.70070","url":null,"abstract":"<p><p>CIC-rearranged sarcoma is a rare, aggressive tumor entity with a dismal outcome. We describe a patient with a history of B-cell acute lymphoblastic leukemia (B-ALL), presenting to our hospital with seizures and left-sided upper limb weakness. Brain imaging revealed a localized right frontal mass, which was surgically resected. Initial pathological analyses suggested a secondary malignant neoplasm, not otherwise specified. However, the tumor's methylome was profiled and analyzed using the DKFZ brain tumor classifier to reach a diagnosis of CIC-rearranged sarcoma, confirmed by FISH study. The patient received the ICE protocol, alongside focal radiotherapy. The patient experienced a local recurrence 14 months post-diagnosis. The brain tumor classifier significantly improved the efficiency of diagnosing this rare tumor in a pediatric patient. However, effective therapeutic regimens for CIC-rearranged sarcomas remain unavailable.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 4","pages":"e70070"},"PeriodicalIF":1.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448445","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}
NeuropathologyPub Date : 2026-08-01DOI: 10.1111/neup.70072
Niloofar Sina, Chris Heyn, Zeina Ghorab, Julia Keith
{"title":"A 13-Year Review of Non-Diffuse Large B Cell Lymphomas of the Central Nervous System at a Tertiary Hospital: A Case Series Study.","authors":"Niloofar Sina, Chris Heyn, Zeina Ghorab, Julia Keith","doi":"10.1111/neup.70072","DOIUrl":"10.1111/neup.70072","url":null,"abstract":"<p><p>Non-diffuse large B-cell lymphomas (non-DLBCL) of the central nervous system (CNS) are rare and diagnostically challenging. This study aims to characterize the clinical, radiological, and pathological features of non-DLBCL CNS lymphomas diagnosed at a tertiary care center over 13 years, highlighting diagnostic pitfalls. A retrospective review was conducted of non-DLBCL CNS lymphoma cases diagnosed at Sunnybrook Health Sciences Centre, Toronto, from 2010 to 2022. Clinical, demographic, and radiological data were extracted from medical records. Imaging was reviewed by a neuroradiologist, and histopathological slides and molecular data were re-evaluated by a pathology team. Additional tests were performed to update classifications per the 5th edition of the WHO Classification of Haematolymphoid Tumors. Seventeen cases were identified (11 males, 6 females; age 38-76), compared to 72 DLBCL cases during the same period. Nine cases were extra-axial and eight intra-axial. Eight were primary and nine secondary CNS lymphomas. B-cell lymphomas (n = 13) included extra-nodal marginal zone lymphoma (n = 6), follicular lymphoma, mantle cell lymphoma, CLL, intravascular large B-cell lymphoma (n = 2), EBV+ LBCL, and polymorphic PTLD. T-cell lymphomas (n = 4) included PTCL, NOS (n = 2), ALK-negative ALCL, and secondary mycosis fungoides. Imaging revealed four major patterns, and symptoms were largely due to mass effect. This case series emphasizes the considerable heterogeneity of non-DLBCL CNS lymphomas and the diagnostic challenges they present. It highlights key features that can aid recognition and improve diagnostic accuracy for these rare CNS entities. Trial Registration: SUN-5771.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 4","pages":"e70072"},"PeriodicalIF":1.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674008","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}
NeuropathologyPub Date : 2026-06-01DOI: 10.1111/neup.70060
Jing Zhou, Sha Zhao, Hai Li, Shudong Yang, Minhong Pan
{"title":"Primary Gliosarcoma With Mesenchymal Differentiation Resembling Follicular Dendritic Cell Sarcoma.","authors":"Jing Zhou, Sha Zhao, Hai Li, Shudong Yang, Minhong Pan","doi":"10.1111/neup.70060","DOIUrl":"10.1111/neup.70060","url":null,"abstract":"<p><p>Gliosarcoma of the central nervous system (CNS) is a rare and aggressive neoplasm exhibiting biphasic differentiation into glial and mesenchymal components. We report a primary gliosarcoma with mesenchymal differentiation resembling follicular dendritic cell sarcoma (FDCS). A 72-year-old man presented with a rim-enhancing lesion in the left frontotemporal parenchyma. Histologically, the tumor was biphasic, comprising a glioblastoma (GBM) component of diffusely infiltrative GFAP- and Olig2-positive oligodendroglial-like cells with microvascular proliferation, and an FDCS component composed of cohesive sheets, nests, and fascicles of CD21-, CD23-, and CD35-positive plump spindle cells. NGS analysis performed on the microdissected components revealed shared PTEN p.N48S mutations with high variant allele frequencies and MGMT promoter methylation, suggesting a monoclonal origin. Furthermore, the two components exhibited divergent genetic profiles: the glial component was characterized by an FGFR1 mutation, PDGFRA fusion, KIT/KDR amplification, and a whole-arm 1p/19q codeletion, whereas the sarcomatous component harbored an ERBB4 p.S853F mutation. These alterations predominantly converged on the RAS-MAPK and PI3K-AKT-mTOR signaling pathways. No IDH1/2 mutations, EGFR gene amplification, or TERT promoter mutations were detected in either component. This case represents the first documented instance of primary gliosarcoma with FDCS differentiation, thereby expanding its known differentiation spectrum. Furthermore, it demonstrates the necessity of separately analyzing each histological component in the diagnosis of challenging cases.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 3","pages":"e70060"},"PeriodicalIF":1.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856430","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 First Autopsy-Proven Case of CSF1R-Related Leukoencephalopathy Harboring the p.Cys774Arg Mutation.","authors":"Hiroyuki Hatsuta, Akitoshi Takeda, Tomomi Fujita, Yuji Nakayama, Kaoru Yagita, Terunori Sano, Taro Shimono, Kaori Sakamoto, Kenichi Kohashi, Ai Obinata, Toshiya Kizaki, Norikazu Hara, Akinori Miyashita, Takeshi Ikeuchi, Yoshiaki Itoh, Masaki Takao","doi":"10.1111/neup.70065","DOIUrl":"10.1111/neup.70065","url":null,"abstract":"<p><p>We report the first autopsy-proven case of colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy harboring the CSF1R mutation c.2320T>C (p.Cys774Arg). The patient, a man in his 40s, exhibited progressive neuropsychiatric symptoms with predominant frontal white matter lesions and corpus callosum atrophy. Neuropathological examination revealed frontal-predominant demyelination with a relatively low number of axonal spheroids compared with typical cases, as well as the absence of intracranial calcifications. In addition, prominent cerebral amyloid angiopathy was observed despite an APOE ε3/ε3 genotype. These findings expand the clinicopathological spectrum of CSF1R-related leukoencephalopathy and highlight variability in pathological features associated with different CSF1R mutations.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 3","pages":"e70065"},"PeriodicalIF":1.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205841","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":"Lymphoplasmacyte-Rich Meningioma: Possible Formation of Intratumoral \"Tertiary Lymphoid Structures\".","authors":"Masayuki Shintaku, Takahiro Hamamoto, Tetsuo Hashiba, Masahiro Nonaka, Takeo Nakaya, Katsunori Uchida, Koji Tsuta","doi":"10.1111/neup.70059","DOIUrl":"10.1111/neup.70059","url":null,"abstract":"<p><p>A surgical case of lymphoplasmacyte-rich (LPR) meningioma that arose in the region of the clivus of an 81-year-old woman is reported. The tumor consisted largely of a dense and diffuse infiltration of mature lymphocytes and a smaller number of plasma cells. Mainly in the peripheral region of the tumor, small sheets or clusters of large polygonal cells having vesicular nuclei and palely eosinophilic cytoplasm were observed. Some of these cells formed cellular whorls. These cells showed immunoreactivity for progesterone receptor, epithelial membrane antigen, somatostatin receptor type 2A, epithelial cadherin, and podoplanin, thus confirming the diagnosis of LPR meningioma. Although lymph follicles having germinal centers were not evident, the distributions of lymphocytes and plasma cells were heterogeneous, and plasma cells occasionally appeared to surround lymphocytic aggregates. Some intratumoral venules showed features of \"high endothelial venules.\" These findings suggested that a dense accumulation of lymphocytes and plasma cells in LPR meningioma was not a simple inflammatory cell infiltration but might represent formation of \"tertiary lymphoid structures.\" Whereas some inflammatory cells showed cytoplasmic immunoreactivity for programmed cell death ligand-1, meningioma cells did not express it.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 3","pages":"e70059"},"PeriodicalIF":1.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840350","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":"Hypertensive Bilateral Thalamic Hemorrhage: Distribution of Ruptured Blood Vessels and Hematoma and Considerations on the Mechanism of Vascular Rupture.","authors":"Shigeki Takeda, Hitoshi Takahashi, Seiichi Hirata, Teruo Miyakawa, Kazunori Yamazaki","doi":"10.1111/neup.70050","DOIUrl":"10.1111/neup.70050","url":null,"abstract":"<p><p>The ruptured blood vessels of a 57-year-old Japanese man who had died 5 days after bilateral hypertensive thalamic hemorrhage (HTH) were investigated by preparing 9 paraffin-embedded tissue blocks, all containing the hematomas. Each block was cut serially into 6-μm-thick sections. The first of every 18 sections was stained with Victoria blue and hematoxylin-eosin, the second with elastica-Goldner, and the third with phosphotungstic acid-hematoxylin. Several additional stainings, including immunostaining for α-smooth muscle actin and synaptophysin, were performed as necessary. In the large hematoma on the right, 18 cross-sections of ruptured blood vessels, comprising 12 arteries and 6 veins, were observed in the area supplied by the thalamoperforate arteries, thalamogeniculate arteries, and some of the posterior choroidal arteries. With an anteroposterior distribution, these ruptured vessels were observed in the middle third to posterior third of the thalamus, with arteries especially concentrated in the middle third. The small hematoma on the left was distributed mainly in the internal capsule. Two cross-sections of ruptured arteries, one of which had ruptured on the internal capsule side, were observed in the lateral part of the ventral posterolateral nucleus of the thalamus. In the hematomas, degeneration of medial smooth muscle cells due to arteriolosclerosis was observed in 14 cross-sections of ruptured arteries encountered, one of which showed a ruptured dissecting aneurysm. Microaneurysm or lipohyalinosis was not evident in any of them as well as the other non-ruptured arteries within the hematomas. The arteries surrounding the hematomas showed fibrinoid degeneration, lipohyalinosis, disruption of the internal elastic lamina, and degeneration and loss of smooth muscle cells in the media. Even though serial sections were examined at the rupture sites, no aneurysm-like structure was found. We concluded that HTH essentially arises from arterial wall fragility due to hypertension, and that aneurysm formation may not be essential.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70050"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276816","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 CNS Neuroblastoma, FOXR2-Activated: Clinicopathological Study of Two Cases With Immunohistochemical Characterization and Literature Review.","authors":"Sumanta Das, Sunita Ahlawat, Komal Agrawal, Salman Shaikh, Rakesh Kumar Gupta, Suman S Karanth, Sandeep Vaishya, Rana Patir, Mehar Chand Sharma","doi":"10.1111/neup.70049","DOIUrl":"10.1111/neup.70049","url":null,"abstract":"<p><p>Primary central nervous system (CNS) neuroblastoma, FOXR2-activated (CNS-NB-FOXR2), is a rare embryonal tumor characterized by neuroblastic differentiation and structural rearrangement of the FOXR2 gene. Previously grouped under CNS primitive neuroectodermal tumors (PNET), this entity has been reclassified based on genome-wide DNA methylation profiling. In this study, we present the detailed clinicopathological and immunohistochemical features of two pediatric cases diagnosed at our center. The first case involved a six-year-old with a left frontal mass; the second was a one-year-old with a large bifrontal lesion. Radiologically, both cases mimicked other embryonal tumors or high-grade gliomas. Histologically, tumors displayed small round blue cell morphology with neuroblastic features, including Homer-Wright rosettes and ganglionic differentiation. Immunohistochemistry demonstrated diffuse positivity for OLIG2, synaptophysin, and L1CAM, with negative expression for GFAP, EMA, and IDH1 R132H. FOXR2 showed nuclear positivity in both cases, supporting the diagnosis. Both cases exhibited diffuse L1CAM positivity-a rare finding with limited evidence in the existing literature. Although DNA methylation profiling could not be performed, the diagnosis was supported by characteristic morphology and immunohistochemistry profile. This report highlights key diagnostic features and potential mimics of CNS neuroblastoma, FOXR2-activated, and underscores the utility of immunohistochemistry in low-resource settings. Recognizing this entity is essential for accurate classification and appropriate therapeutic planning. Further studies are warranted to explore targeted therapies, including MEK inhibitors, which may hold promise based on emerging molecular data.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70049"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290614","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}
NeuropathologyPub Date : 2026-04-01DOI: 10.1111/neup.70051
Seiichi Hirata, Hitoshi Takahashi, Shigeki Takeda
{"title":"An Attempt of a Staining Method to Clarify the Localization of Hematomas in Autopsy Cases of Intracerebral Hemorrhage: Application of Double Staining With Immunohistochemistry for Anti-Synaptophysin Antibody Using DAB-CoCl<sub>2</sub> and EA50.","authors":"Seiichi Hirata, Hitoshi Takahashi, Shigeki Takeda","doi":"10.1111/neup.70051","DOIUrl":"10.1111/neup.70051","url":null,"abstract":"<p><p>In order to prepare specimens to clarify the anatomical localization of intracerebral hematomas (ICHs), we examined 18 autopsy cases ranging from 1 day to 2.5 months after onset: Five cases of hypertensive ICH (two cases of putaminal hematoma, one case of thalamic hematoma, one case of mixed-type hematoma, and one case of cerebellar hematoma), two cases of subarachnoid hemorrhage with ICH, three cases of cerebral amyloid angiopathy-related hemorrhage, two cases of ICH associated with blood coagulation abnormalities, and six cases of brain death with ICH (brain death period: 10 h to 13 days). Paraffin blocks containing hematomas that have hardened and have poor formalin penetration can be easily sectioned at 6 μm thickness by using Histoheme, an ammonia-based softening reagent. By mounting the sections on MAS-coated glass slides or New Silan III-coated glass slides, we were able to minimize the peeling of hematomas from the slides. Conventional staining (Klüver-Barrera staining, Elastica-Masson Goldner staining) showed decreased staining of the brain tissue surrounding the hematoma due to the effects of edema, making the localization of the hematoma unclear. Synaptophysin (SYP) immunostaining was visualized with 3,3'-diaminobenzidine tetrahydrochloride (DAB)-CoCl<sub>2</sub> and double stained with eosin azur 50 (EA50) (DAB-CoCl<sub>2</sub> SYP + EA50). This method revealed gray matter as black and fresh to relatively recent hematoma as red, and clearly demonstrated the anatomical localization of the hematoma without any reduction in staining due to edema. In contrast, hematomas in cases more than 29 days after onset showed heterogeneous staining in red or green, and the boundary between the brain tissue and the hematoma was unclear. However, with double staining using DAB-CoCl<sub>2</sub> SYP and Masson Goldner staining, the hematoma stained dark red, and the boundary with the brain tissue was more clearly visible than with DAB-CoCl<sub>2</sub> SYP + EA50.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70051"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284521","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}