Journal of Pathology and Translational Medicine

Original Article

Single-center study on clinicopathological and typical molecular pathologic features of metastatic brain tumor: Su Hwa Kim, Young Suk Lee, Sung Hak Lee, Yeoun Eun Sung, Ahwon Lee, Jun Kang, Jae-Sung Park, Sin Soo Jeun, Youn Soo Lee; J Pathol Transl Med. 2023;57(4):217-231. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.10

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Abstract PDF: Background
The metastatic brain tumor is the most common brain tumor. The aim of this study was to demonstrate the clinicopathological and molecular pathologic features of brain metastases (BM).
Methods
A total of 269 patients were diagnosed with BM through surgical resection at Seoul St. Mary’s Hospital from January 2010 to March 2020. We reviewed the clinicopathological features and molecular status of primary and metastatic brain tissues using immunohistochemistry and molecular pathology results.
Results
Among 269 patients, 139 males and 130 females were included. The median age of primary tumor was 58 years (range, 13 to 87 years) and 86 patients (32.0%) had BM at initial presentation. Median BM free interval was 28.0 months (range, 1 to 286 months). The most frequent primary site was lung 46.5% (125/269), and followed by breast 15.6% (42/269), colorectum 10.0% (27/269). Epidermal growth factor receptor (EGFR) mutation was found in 50.8% (32/63) and 58.0% (40/69) of lung primary and BM, respectively. In both breast primary and breast cancer with BM, luminal B was the most frequent subtype at 37.9% (11/29) and 42.9% (18/42), respectively, followed by human epidermal growth factor receptor 2 with 31.0% (9/29) and 33.3% (14/42). Triple-negative was 20.7% (6/29) and 16.7% (7/42), and luminal A was 10.3% (3/29) and 7.1% (3/42) of breast primary and BM, respectively. In colorectal primary and colorectal cancer with BM, KRAS mutation was found in 76.9% (10/13) and 66.7% (2/3), respectively.
Conclusions
We report the clinicopathological and molecular pathologic features of BM that can provide useful information for understanding the pathogenesis of metastasis and for clinical trials based on the tumor’s molecular pathology.

Reviews

Neuropathologic features of central nervous system hemangioblastoma: Rebecca A. Yoda, Patrick J. Cimino; J Pathol Transl Med. 2022;56(3):115-125. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.04.13

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Hemangioblastoma is a benign, highly vascularized neoplasm of the central nervous system (CNS). This tumor is associated with loss of function of the VHL gene and demonstrates frequent occurrence in von Hippel-Lindau (VHL) disease. While this entity is designated CNS World Health Organization grade 1, due to its predilection for the cerebellum, brainstem, and spinal cord, it is still an important cause of morbidity and mortality in affected patients. Recognition and accurate diagnosis of hemangioblastoma is essential for the practice of surgical neuropathology. Other CNS neoplasms, including several tumors associated with VHL disease, may present as histologic mimics, making diagnosis challenging. We outline key clinical and radiologic features, pathophysiology, treatment modalities, and prognostic information for hemangioblastoma, and provide a thorough review of the gross, microscopic, immunophenotypic, and molecular features used to guide diagnosis.

Citations

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Molecular Testing of Brain Tumor: Sung-Hye Park, Jaekyung Won, Seong-Ik Kim, Yujin Lee, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi; J Pathol Transl Med. 2017;51(3):205-223. Published online May 12, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.08

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Abstract PDF

The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53, and ATRX, oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC, FUBP1, and the promoter region of telomerase reverse transcriptase (TERTp). IDH-wildtype (primary) glioblastomas typically lack mutations in IDH, but are characterized by copy number variations of EGFR, PTEN, CDKN2A/B, PDGFRA, and NF1 as well as mutations of TERTp. High-grade pediatric gliomas differ from those of adult gliomas, consisting of mutations in H3F3A, ATRX, and DAXX, but not in IDH genes. In contrast, well-circumscribed low-grade neuroepithelial tumors in children, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma, often have mutations or activating rearrangements in the BRAF, FGFR1, and MYB genes. Other CNS tumors, such as ependymomas, neuronal and glioneuronal tumors, embryonal tumors, meningothelial, and other mesenchymal tumors have important genetic alterations, many of which are diagnostic, prognostic, and predictive markers and therapeutic targets. Therefore, the neuropathological evaluation of brain tumors is increasingly dependent on molecular genetic tests for proper classification, prediction of biological behavior and patient management. Identifying these gene abnormalities requires cost-effective and high-throughput testing, such as next-generation sequencing. Overall, this paper reviews the global guidelines and diagnostic algorithms for molecular genetic testing of brain tumors.

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Case Reports

Chondromyxoid Fibroma of the Ethmoid Sinus Complicated by a Brain Abscess: A Case Report and Literature Review.: Kyu Yeoun Won, Juhie Lee, Youn Wha Kim, Eui Jong Kim, Sung Wan Kim, Yong Koo Park; Korean J Pathol. 2010;44(5):547-550.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.547

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Abstract PDF

Chondromyxoid fibroma (CMF) is a relatively rare bone tumor that was first described by Jaffe and Lichtenstein in 1948. CMF of the sinonasal tract is very rare. A 28-year-old male presented with long-standing, intermittent, pulsatile pain in the right temporal area. A computed tomography scan showed a 20 x 19 mm round, bony density in the right ethmoid sinus with fluid collection in the ethmoid and frontal sinuses. Additionally, a cystic lesion with surrounding edema was found in the right frontal lobe. The patient underwent a partial ethmoidectomy and frontostomy. A histological examination showed polygonal and stellate cells in a myxoid and chondroid background with a pattern of lobulation and plaque-like calcification. The bone lesion was revealed as a CMF of the ethmoidal sinus, and the frontal lobe cystic lesion was a brain abscess associated with the CMF. We present the case of a CMF of the ethmoid sinus complicated by a brain abscess.

Citations

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Juxtacortical chondromyxoid fibroma in the small bones: two cases with unusual location and a literature review
Sun-Ju Oh, So Hak Chung
Journal of Pathology and Translational Medicine.2022; 56(3): 157. CrossRef
Treatment of cryotherapy and orthotopic transplantation following chondromyxoid fibroma of zygomatic bone
Zhi-Chao Zhu, Yi-Fei Yang, Xu Yang, Yan Liu, Yi-nan Cheng, Zhao-Yao Sun, Tian-Shu Xu, Wen-Jun Yang
Medicine.2018; 97(31): e11707. CrossRef

Malignant Glomus Tumors of the Stomach: A Report of 2 Cases with Multiple Metastases.: Hyunjoo Lee, Yoon Seok Choi, Sang Cheul Oh, Jong Jae Park, Chul Whan Kim, Han Kyeom Kim, Insun Kim; Korean J Pathol. 2009;43(4):358-363.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.358

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Abstract PDF

Glomus tumors are mesenchymal neoplasms usually developing in the dermis or subcutis of the extremities. The majority of glomus tumors are entirely benign, and malignant glomus tumors are very rare, especially those arising in the visceral organs. Here, we are presenting two cases of malignant glomus tumor, initially diagnosed in the stomach by endoscopic biopsy. Case 1 was found in the stomach, right kidney, brain and humerus of a 65-year-old woman, and Case 2 in the stomach and liver of a 63-year-old man. Histologically, the tumor was composed of solid sheets and nests of round and short-spindle shaped tumor cells with vesicular nucleus and prominent nucleolus. The tumor cells were closely admixed with blood vessels of varying size. Immunohistochemically, the tumor cells showed diffuse and strong positive staining for smooth muscle actin and paranuclear, dot-like staining for synaptophysin, but negative for desmin, c-kit, CD34 and S-100 protein. These two are rare cases of a malignant glomus tumor with widespread metastases.

Citations

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Clinicopathologic features of gastric glomus tumor: A report of 15 cases and literature review
Minying Deng, Rongkui Luo, Jie Huang, Yuanlong Luo, Qi Song, Huaiyu Liang, Chen Xu, Wei Yuan, Yingyong Hou
Pathology and Oncology Research.2023;[Epub] CrossRef
Glomus Tumor of the Stomach: A Systematic Review and Illustrative Case Report
Andrea Pansa, Laura Samà, Laura Ruspi, Federico Sicoli, Ferdinando Carlo Maria Cananzi, Vittorio Quagliuolo
Digestive Diseases.2023; 41(1): 17. CrossRef
Locally Advanced Glomus Tumor of the Stomach With Synchronous Liver Metastases: Case Report and Literature Review
Fabio Frosio, Carmine Petruzziello, Elia Poiasina, Michele Pisano, Alessandro Lucianetti
Cureus.2023;[Epub] CrossRef
Gastric Glomus Tumor: A Clinicopathologic and Immunohistochemical Study of 21 Cases
Jun Lin, Juan Shen, Hao Yue, Qiongqiong Li, Yuqing Cheng, Mengyun Zhou
BioMed Research International.2020; 2020: 1. CrossRef
Malignant glomus tumor of the gastric antrum with hepatic metastases: a case report and literature review
Adina A. Bodolan, Rebecca Wilcox, Michelle X. Yang
Human Pathology: Case Reports.2018; 14: 81. CrossRef

Nasal Cerebral Heterotopia-so called Nasal Glioma: A case report.: Tae Sook Kim, Je G Chi; Korean J Pathol. 1995;29(4):517-520.

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Abstract PDF: Encephalocele and nasal glioma are rare, benign congenital neuroectodennal tumors which result from a failure of embryologic sepearation of neuroectodermal and ectodemlal tissues. Nasal glioma should be differentiated from a true glioma, and from a primary encephalocele, which is a herniation of the cranial contents through a bony defect in the skull. For this reason, nasal cerebral heterotopia is a preferred term. We report an unusual case of a nasal mass that was histologically indistinguishable from nasal cerebral heterotopia but proved to be connected to the skull base by fibrotic cord. The patient was a 2 year old girl who had had a slow growing palpable mass in the left epicanthal area for three months.

Alzheimer's Disease: Report of two cases.: Hee Sung Kim, Yeon Lim Suh, Kyung Sue Hong, Duk Lyul Na; Korean J Pathol. 1997;31(2):167-173.

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Abstract PDF: Alzheimer's disease (AD) is the most common etiology of dementia, that has not been previously reported in Korea. We have experienced two cases of Alzheimer's disease, one occurred in a 53-year-old man with dementia and the other occurred in a 36-year-old woman with a family history of early onset dementia. A neocortical biopsy was done to rule out the cause of dementia and showed diffusely scattered numerous senile plaques and neurofibrillary tangles in cortex of both cases. Interestingly, GFAP, an immunohistochemical stain showed strong positivity in neuritic plaques and the surrounding fibrillary gathering.

Original Article

p53 Expression and Ki-67 Labeling Index in Brain Tumor with Special Reference to Tumor and Histologic Grade.: Duck Hwan Kim, Yeon Lim Suh, Dong Ik Shin, Hyung Jin Shin, Jong Hyun Kim; Korean J Pathol. 1998;32(2):81-87.

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Abstract PDF: Mutation in the p53 suppressor gene is the most common genetic alteration found in human cancers including primary brain tumors. Ki-67 labeling index(LI) is known to be a marker of proliferating activity. The purpose of this study was to verify whether an immunohistochemical expression of p53 antibody and Ki-67 LI could be related to different clinicopathologic parameters including histologic grade, size, invasiveness and recurrence of the brain tumors. Materials were based on the 147 surgically resected brain tumors during the last two years. Of the 147 brain tumors, there were 35 astrocytic tumors, 35 meningiomas, 10 oligodendrogliomas, 7 craniopharyngiomas, 5 dysembryoplastic neuroepithelial tumors, 4 medulloblastomas, 5 ependymomas, 23 pituitary adenomas, 9 schwannomas, and 14 other brain tumors. The p53 expression and Ki-67 LI were higher in malignant brain tumors including astrocytic tumors, medulloblastoma, PNET and gliosarcoma. The p53 positivity was correlated with histologic grades and tumor recurrence. The brain tumors with a high Ki-67 LI(>6%) also showed a close relationship to a higher histologic grading, radiological invasiveness and recurrence. There was no evident correlation with the age and tumor size with p53 expression and Ki-67 LI. These results suggest that p53 overexpression and high proliferation potential of the tumor cells are associated with the higher histologic grade and aggressive clinical course in the central nervous system tumors.

Case Report

Mixed Gangliocytoma-Pituitary Adenoma: A case report.: Dong Sug Kim, Dae Hong Suh, Mi Jin Kim, O Lyong Kim; Korean J Pathol. 1998;32(2):138-141.

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Abstract PDF: The mixed gangliocytoma-pituitary adenoma is a very rare intracranial neoplasm, and it is frequently associated with endocrine symptoms; acromegaly, Cushing's disease, galactorrhea and amenorrhea. Morphologically it shows a mixture of gangliocytoma and pituitary adenoma in various proportions. In the area of gangliocytoma, there is no neoplastic glial component. The portion of pituitary adenoma consists mainly of chromophobe cells. There are three hypotheses in its histogenesis. We report a case of a 41 year-old lady presented with acromegaly and amenorrhea existing for 3 years. On magnetic resonance image, there is a dumbell-shaped mass in the sellar region. Histologically it showed typical features of mixed gangliocytoma-pituitary adenoma. This case is presented in the view of its rarity and interesting possible histogeneses.

Original Article

The Diagnostic Significance of AgNORs and MIB-1 Labelling Index in Atypical Meningioma.: Dae Hong Suh, Dong Sug Kim, Oh Lyong Kim; Korean J Pathol. 1998;32(11):1008-1014.

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Abstract: There is no definite histological criteria which can predict the biologic behavior of meningiomas, although resectability is the most important factor in terms of recurrence. For grading meningiomas, various factors have been studied, such as hypercellularity, nuclear pleomorphism, small cells with high N/C ratio, prominent nucleoli (PN), frequent mitosis, loss of architecture, focal necrosis (FN). We investigated 116 meningiomas to evaluate the correlation between the factors and the proliferative activity using AgNORs and MIB-1 labelling index (LI). They were divided into 3 groups: Group A includes meningiomas with none of the factors; group B with one of the factors; group C with two or more factors. MIB-1 LI was correlated with each factor, but AgNORs was not. There was a statistical difference among group A (<1.28%), B (2.7%) and C (5.1%) (p<0.05) using MIB-1 LI. FN was the most frequently associated with other factors, and it had the highest MIB-1 LI (6.31%). MIB-1 LI of group B was 5.1 2.3%. In group B, the most frequent combination was FN and PN, and it showed the highest MIB-1 LI (5.74%). This study indicates that FN and PN are important for diagnosis of atypical meningioma, and MIB-1 LI appears to be a useful method for estimating the proliferative activity of meningiomas, and 5% or more of MIB-1 LI could help in making a diagnosis of atypical meningioma.

Case Report

Heterotopic Brain Tissue in the Soft Palate.: Hyun Joo Choi, Youn Soo Lee, Young Shin Kim, Kyo Young Kim, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1998;32(11):1039-1041.

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Abstract: Heterotopic brain tissue is a developmental anomaly of neurogenic origin with no malignant potential, and is usually present around the nose of children and infants. So it has been called nasal glioma. But, even more rarely, heterotopic glial tissue may be found in various sites other than nasal cavity, such as the ethmoidal sinus, palate, tonsillar area, pharynx, ear, subcutaneous tissue, lung, and female genital tract. We experienced a more unusual case of a polypoid heterotopic brain tissue in the soft palate in a 3-year-old boy. The mass was microscopically reminiscent of "gliosis" of the central nervous system and interestingly contained choroid plexus focally. The glial nature of the lesion was confirmed by glial fibrillary acidic protein immunostain.

Original Articles

Abnormal Development and Apoptosis Observed in Brains of the Trisomy 16 Mouse.: Eun youn Cho, Yeon Lim Suh, Je Geun Chi; Korean J Pathol. 1999;33(8):570-580.

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Abstract PDF: We have studied morphologic characteristics and apoptosis on the fetal brain of the trisomy 16 mouse, a model for human trisomy 21 syndrome. This study was based on serial sections of the whole brain from a sample of sixteen trisomy 16 mice and forty-six age-matched control littermates from embryonic day (ED) 12 to ED 18. Trisomy 16 brains showed a reduction of telencephalic size and abnormal cortical development. At ED 13 trisomy 16 and control brains appeared similar. By ED 14 difference in the cortical thickness and telencephalic growth became evident, and by ED 16 a marked size difference had developed between the trisomy 16 and control brains. By ED 18, however, the thickness of the trisomy 16 cortex had increased considerably and was not significantly different with respect to the thickness and cross-sectional areas of the pallium and its constituent cortical layers. The cell density of the trisomy 16 cortex had persistently decreased before ED 17, when the cell density of control and trisomy 16 corteces was similar within each layer. At ED 18 cell density of trisomy 16 cortex in each layer increased. There was inverse relationship between a number of TUNEL positive apoptotic cells and cell density in the trisomy 16 brains. Our results suggest that developmental abnormalities of the trisomy 16 brain indicated developmental delay of the telencephalon growth, which may be caused by apoptosis rather than by a proliferation defect.

Manganese Intoxication in the Rat A neuropathologic study and distribution of manganese in rat brain.: Tae Jung Jang, Jung Ran Kim, Jong Im Lee, Dong Hoon Kim, Ki Kwon Kim, Ji Yong Kim, Hae Kwan Cheong, Hyun Sul Lim; Korean J Pathol. 1999;33(9):662-674.

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Abstract PDF: We investigated a topographical distribution of managanese, and immunohistochemical density of tyrosine hydroxylase (TH), and histopathologic findings in globus pallidus and substantia nigra according to manganese dose and time course in the brain of rats which received MnCl2 intravenously. Topographical distribution of manganese was also investigated after injection of FeCl2. The manganese concentrations of brain in control and experimental group were highest in pituitary gland and thalamus, and lowest in the cerebral cortex. The manganese concentration of blood was increased proportionally to the dose administered, and the biological half-life of blood manganese was between 21 and 42 days. The manganese concentrations of brain were increased proportionally to the dose, and increase rate was highest in olfactory bulb, and the biological half-lives of brain manganese ranged from 42 days to 90 or more days; the longest were observed in pituitary gland, medulla oblongata and cerebral cortex. In case of administration of FeCl2, the manganese concentrations of brain were higher than that of control group in dose of 2.5 mg/kg, and decreased proportionally to the administered dose, resulting in lower level compared with control group in high dose of FeCl2 administered. Significantly decreased number of nerve cell and increased gliosis in globus pallidus were observed in experimental group, which were closely correlated with the duration after manganese injection, but no significant change of number of nerve cell expressing TH and gliosis were observed in substantia nigra. Density of immunohistochemical reaction for TH in globus pallidus made little difference between control and experimental group. These results suggest that pathology of manganese intoxication is caused by the loss of nerve cells in globus pallidus, and closely correlated with the duration after manganese exposure.

Expression of Laminin Chains in the Neuronal Cells of Mouse Brain.: Gi Jin Kim, Yong Jin Choi, Suk Keun Lee, Je Geun Chi; Korean J Pathol. 1999;33(12):1163-1174.

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Abstract PDF: Laminin-1 is biologically active and can effect cellular proliferation, differentiation, migration, and apoptosis. In the central nervous system, neuronal cells are rarely reported to give positive reaction by laminin antibody staining. However, the original cell type which can produce the laminin molecule has not been well established. Since the neuronal cells of brain are derived from neuroectoderm, we thought that the neuronal cells should be able to produce the laminin molecules as other epithelial cells. In this study we aimed to explore whether the neuronal cells express the laminin chain mRNAs, and further to identify which types of laminin isoform are expressed at the specific sites of the brain structure. We found that neuronal cell was the important cell type in mouse brain, which could produce laminin isoforms. Although immunostainings disclosed reactivity of laminins in the basement membrane of capillaries as well as neuronal cells, mRNA expressions of laminins were intense only in the neuronal cells. It was relatively weak in the endothelial cells. Among neuronal cells the cortical cells of cerebrum, pyramidal cells of hippocampus, and Purkinje cells of cerebellum showed pronounced expression of laminin chain mRNA. Glial cells, especially astrocytes, were negative for laminin subtypes both in immunohistochemistry and in situ hybridization. Taken together, our data indicate that the neuronal cells of mouse brain actively produce laminin isoforms, and the resultant polymerized laminins are accumulated mainly in the basement membrane of capillaries. In conclusion, the results indicate that neuronal cells produce and utilize the different laminin chains to maintain the neurovascular environment of brain.

Histopathologic Change and Apoptotic Profile in Basal Ganglia of Rat Induced by Manganese Administration.: Chang Won Ha, Jong Im Lee, Jung Ran Kim, Tae Jung Jang, Ki Kwon Kim, Dong Hoon Kim; Korean J Pathol. 2000;34(6):419-430.

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Abstract PDF: Mn (manganese) is known to induce Parkinsonian neurological disorder. Several lines of evidence suggest that apoptosis is involved not only in physiological cell death during normal development but also in neurodegenerative disease. The mechanism of Mn induced cell death remains poorly understood. In the present study, we evaluated the morphologic changes and apoptotic profile in basal ganglia using rat model of Mn toxicity. The rats were divided into three groups: the first group was a control; the second group was subdivided by administration dosage of Mn into group A (5, 10 mg MnC12/ kg) and group B (20, 40 mg MnC12/kg). The rats of each subgroup received a injection of Mn via tail vein every week for 4 weeks. The second group received 4 repeated injection of 10 mg MnC12/kg in the same manner and the rats were sacrificed at day 1, 3 & 7 in group I and at day 10, 21, 42, and 90 in group II after the last injection. A significant loss of neuron and gliosis were observed in the basal ganglia in the experimental groups (p<0.05), which were more pronounced in group II than in the control or group I. No significant difference in number of nerve cells or degree of gliosis was identified in the substantia nigra. Apoptotic cells were also increased in basal ganglia of experimental groups and appeared among neurons (10%), glial cells (10%), and endothelial cells (60%). Apoptotic figures were consistently noted through the entire experimental period after Mn injection in basal ganglia. In conclusion, these results demonstrate that Mn-induced cytopathic insult affects various cell types in basal ganglia and shows variable sensitivity in the different regions of brain, especially in the apoptotic cell death of the neuron. The overaccumulation of Mn in the brain might be attributed from the breakdown of blood-brain barrier due to the injury through the apoptosis.

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