K. Amita, T. Rajini, M. Sanjay, M. Abhishek, K. Prashantha
Abstract Introduction. Hydatid cyst, caused by Echinococcus granulosa, occurs rarely in the musculoskeletal region. Most of the time, clinically and radiologically it is diagnosed as a soft tissue tumor, benign or malignant. There are a few case reports of hydatid cyst presenting as an intramuscular thigh mass, which has been diagnosed at fine needle aspiration cytology (FNAC). Accurate pre-operative diagnosis is essential in view of specific therapeutic options for this disease. Here we report a case of hydatid cyst occurring in an unusual location (thigh) and masquerading as a soft tissue tumour, diagnosed at FNAC. Case Report. 56-year-old male patient presented with gradually increasing swelling of the left thigh since 3 years. On examination, there was a firm non-tender 25 × 20 cm swelling on the posterior aspect of left thigh extending from the gluteal region to five cm above the knee joint. An ultrasound diagnosis of a soft tissue tumor was made. At FNAC, fluid was aspirated and smears showed granulomas along with multiple hyaline acellular membrane-like fragments, few showing vague laminations. A diagnosis of hydatid cyst was made at FNAC which was corroborated at histopathology. Conclusion. Intramuscular hydatid cyst of the thigh is a very rare manifestation. The possibility of hydatid cyst should be considered while aspirating any soft tissue mass lesion, especially when fluid is obtained and microscopy shows acellular hyaline membrane-like material, even when fewer laminations are noted.
{"title":"Intramuscular hydatid cyst of thigh masquerading as a soft tissue tumour diagnosed by fine needle aspiration cytology","authors":"K. Amita, T. Rajini, M. Sanjay, M. Abhishek, K. Prashantha","doi":"10.1515/ersc-2021-0003","DOIUrl":"https://doi.org/10.1515/ersc-2021-0003","url":null,"abstract":"Abstract Introduction. Hydatid cyst, caused by Echinococcus granulosa, occurs rarely in the musculoskeletal region. Most of the time, clinically and radiologically it is diagnosed as a soft tissue tumor, benign or malignant. There are a few case reports of hydatid cyst presenting as an intramuscular thigh mass, which has been diagnosed at fine needle aspiration cytology (FNAC). Accurate pre-operative diagnosis is essential in view of specific therapeutic options for this disease. Here we report a case of hydatid cyst occurring in an unusual location (thigh) and masquerading as a soft tissue tumour, diagnosed at FNAC. Case Report. 56-year-old male patient presented with gradually increasing swelling of the left thigh since 3 years. On examination, there was a firm non-tender 25 × 20 cm swelling on the posterior aspect of left thigh extending from the gluteal region to five cm above the knee joint. An ultrasound diagnosis of a soft tissue tumor was made. At FNAC, fluid was aspirated and smears showed granulomas along with multiple hyaline acellular membrane-like fragments, few showing vague laminations. A diagnosis of hydatid cyst was made at FNAC which was corroborated at histopathology. Conclusion. Intramuscular hydatid cyst of the thigh is a very rare manifestation. The possibility of hydatid cyst should be considered while aspirating any soft tissue mass lesion, especially when fluid is obtained and microscopy shows acellular hyaline membrane-like material, even when fewer laminations are noted.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"64 1","pages":"15 - 19"},"PeriodicalIF":0.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76862505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objectives: Rhinoscleroma is a rare infectious disease of the upper respiratory tract caused by Klebsiella rhinoscleromatis. Apart from mandating an appropriate antibiotic therapy, it poses a unique challenge to the pathologists since it can clinically simulate a malignancy. The main objective was to study the cases of rhinoscleroma of the respiratory tract in a period of 3 years with an emphasis on the clinico-pathologic features. Methods: We report a retrospective analysis of 7 cases, histopathologically diagnosed at our centre as rhino-scleroma. The topography ranged from nasal mucosa (3), pharynx (2) and larynx (2). Results: Histopathological examination in all cases showed diffuse aggregates of foamy macrophages (Mikulicz cells) containing intracytoplasmic basophilic organisms; admixed with plasma cells in a fibrotic stroma. The overlying epithelium appeared atrophic to focally hyperplastic. The age ranged from 36–67 years, involving both genders. The significant clinical history included a nasal block without anosmia, atrophic rhinitis with septal perforation to subglottic stenosis, requiring immediate surgical intervention. In 4 of the 7 cases, the working clinical diagnosis was stipulated as a malignancy. Conclusions: Rhinoscleroma can affect different regions in the upper aero digestive tract. A lack of awareness and a delay in the diagnosis of this disease can lead to complications including upper airway obstruction, physical deformity, and rarely, sepsis. In addition, it must be remembered that the treatment of rhinoscleroma is challenging and requires a prolonged course of antibiotics to achieve a definite cure and avoid relapses.
{"title":"Rhinoscleroma – A unique masquerader. A retrospective case series","authors":"D. Nayak M, L. Shenoy","doi":"10.1515/ersc-2021-0001","DOIUrl":"https://doi.org/10.1515/ersc-2021-0001","url":null,"abstract":"Abstract Objectives: Rhinoscleroma is a rare infectious disease of the upper respiratory tract caused by Klebsiella rhinoscleromatis. Apart from mandating an appropriate antibiotic therapy, it poses a unique challenge to the pathologists since it can clinically simulate a malignancy. The main objective was to study the cases of rhinoscleroma of the respiratory tract in a period of 3 years with an emphasis on the clinico-pathologic features. Methods: We report a retrospective analysis of 7 cases, histopathologically diagnosed at our centre as rhino-scleroma. The topography ranged from nasal mucosa (3), pharynx (2) and larynx (2). Results: Histopathological examination in all cases showed diffuse aggregates of foamy macrophages (Mikulicz cells) containing intracytoplasmic basophilic organisms; admixed with plasma cells in a fibrotic stroma. The overlying epithelium appeared atrophic to focally hyperplastic. The age ranged from 36–67 years, involving both genders. The significant clinical history included a nasal block without anosmia, atrophic rhinitis with septal perforation to subglottic stenosis, requiring immediate surgical intervention. In 4 of the 7 cases, the working clinical diagnosis was stipulated as a malignancy. Conclusions: Rhinoscleroma can affect different regions in the upper aero digestive tract. A lack of awareness and a delay in the diagnosis of this disease can lead to complications including upper airway obstruction, physical deformity, and rarely, sepsis. In addition, it must be remembered that the treatment of rhinoscleroma is challenging and requires a prolonged course of antibiotics to achieve a definite cure and avoid relapses.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"16 1","pages":"1 - 6"},"PeriodicalIF":0.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77520244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Background: Some investigations show that obesity is associated with increase in bone mass due to excessive mechanical exertion. However, these data are contradictory as loss of mineral density of bone tissue and, respectively, the risk of fractures in this population group is higher. The aim of the research was to investigate impact of drug therapy with zoledronic acid on nanostructure of bones in rats with limited mobility and high-calorie diet. Methods: Rats (n = 56) were distributed into three groups: control (n = 18) – standard vivarium conditions, І experimental group (n = 18) – rats, which were on a high-calorie diet with limited mobility (HCD+LM), ІІ experimental group (n = 18) – HCD+LM+zoledronic acid. Zoledronic acid was injected at the dose 0.025 mg/kg intramuscularly every four weeks for six months. X-ray structure analysis, scanning electron microscopy and atomic absorption spectrometry were used for investigation of ultrastructure and quantitative assessment of mineral component loss in the femoral neck. Results: Obesity and limited mobility reduced the level of the mineral component in the femoral neck (−31.5%) compared with control. It is significant that zoledronic acid did not permit decrease in mineral component of the bone throughout the entire experiment compared with group I (+41.8%), and all parameters were higher than in control group (+15%). Conclusions: Obesity and limited mobility negatively affect mineral bone mass. Zoledronic acid induces increase in the mineral component as a result of remodeling inhibition under conditions of obesity and limited mobility modeling.
{"title":"Effects of zoledronic acid on bone structure and organization of nanocomposites in rats with obesity and limited mobility","authors":"N. Kostyshyn, I. Shtablavyi","doi":"10.1515/ersc-2021-0002","DOIUrl":"https://doi.org/10.1515/ersc-2021-0002","url":null,"abstract":"Abstract Background: Some investigations show that obesity is associated with increase in bone mass due to excessive mechanical exertion. However, these data are contradictory as loss of mineral density of bone tissue and, respectively, the risk of fractures in this population group is higher. The aim of the research was to investigate impact of drug therapy with zoledronic acid on nanostructure of bones in rats with limited mobility and high-calorie diet. Methods: Rats (n = 56) were distributed into three groups: control (n = 18) – standard vivarium conditions, І experimental group (n = 18) – rats, which were on a high-calorie diet with limited mobility (HCD+LM), ІІ experimental group (n = 18) – HCD+LM+zoledronic acid. Zoledronic acid was injected at the dose 0.025 mg/kg intramuscularly every four weeks for six months. X-ray structure analysis, scanning electron microscopy and atomic absorption spectrometry were used for investigation of ultrastructure and quantitative assessment of mineral component loss in the femoral neck. Results: Obesity and limited mobility reduced the level of the mineral component in the femoral neck (−31.5%) compared with control. It is significant that zoledronic acid did not permit decrease in mineral component of the bone throughout the entire experiment compared with group I (+41.8%), and all parameters were higher than in control group (+15%). Conclusions: Obesity and limited mobility negatively affect mineral bone mass. Zoledronic acid induces increase in the mineral component as a result of remodeling inhibition under conditions of obesity and limited mobility modeling.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"14 1","pages":"7 - 14"},"PeriodicalIF":0.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81908174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In an elegantly presented and thought-provoking manuscript published by the journal Radiotherapy and Oncology, Valstar et al. characterize previously unreported structures comprising salivary gland tissue near the torus tubarius [1]. The authors present their findings in three stages. First, they identify these entities in patients with prostate or urethral gland cancer who underwent positron emission tomography / computed tomography with prostate-specific membrane antigen ligands (PSMA PET/ CT), which technique—despite its name—demonstrates avidity for salivary glands. The investigators then evaluate these glands using human cadavers, and finally assess the effect of radiation therapy involving this region in head & neck cancer (HNC) patients. Ultimately, the authors proffer two conclusions from their findings. First, they propose recognition of this region as newly identified paired organs, suggesting the designation of “tubarial glands.” Second, they underscore the importance of sparing this area from the toxic effects of radiation therapy, to whatever extent feasible. Whereas the second of these points seems more resonant and straightforward, the authors appear to emphasize the first, in terms of coverage and explication. The dichotomy between these claims, and the relative prominence of the purported anatomic contribution within the manuscript, potentially detract from study’s significant clinical impact. The anatomic issue—whether these glands more closely resemble major or minor salivary glands—is an interesting question. In terms of features shared in common with major glands, the authors discuss several analogies between the tubarial glands and sublingual glands. For instance, the tubarial glands lack a capsule, and the sublingual glands show only partial encapsulation. The authors also demonstrate the tubarial glands’ “multiple macroscopically visible draining duct openings in the dorsolateral pharyngeal wall” in Figure 4. The sublingual gland secretes its products through multiple ducts as well. However, these features (absence of a fibrous capsule, and presence of multiple ducts) pertain to minor salivary glands as well as the sublingual gland, and therefore may not distinguish the tubarial glands as major versus minor. Conversely, the tubarial glands exhibit several aspects analogous to the minor salivary glands of the palate, potentially suggesting a designation as minor rather than major glands for the region in question. The authors concede these resemblances, stating “the tubarial glands have many similarities with the palatal conglomerate of microscopic glands.” From the perspective of a pathologist, anyway (and based on the text), the relationship between the radiologic features of the tubarial and palatal glands is difficult to discern. The authors alternately describe the PET avidity of the tubarial glands as “consistently more than the uptake in the palate,” and/or as “comparable to the mucous aspect and PSMA-ligand uptake o
在《放射治疗与肿瘤学》杂志上发表的一篇优雅且发人深省的手稿中，Valstar等人描述了以前未报道的结构，包括输卵管环部附近的唾液腺组织[1]。作者将他们的发现分为三个阶段。首先，他们在接受前列腺特异性膜抗原配体正电子发射断层扫描/计算机断层扫描(PSMA PET/ CT)的前列腺癌或尿道癌患者中识别出这些实体，该技术-尽管其名称-显示了唾液腺的贪婪。研究人员随后用人体尸体对这些腺体进行了评估，并最终评估了头颈癌(HNC)患者放射治疗对该区域的影响。最后，作者从他们的发现中得出了两个结论。首先，他们建议将这一区域视为新发现的成对器官，建议将其命名为“输卵管腺”。其次，它们强调了在任何可行的范围内使该区域免受放射治疗毒性影响的重要性。虽然第二点似乎更能引起共鸣，也更直接，但作者似乎在覆盖和解释方面强调了第一点。这些说法之间的二分法，以及在手稿中相对突出的所谓解剖学贡献，可能会削弱研究的重大临床影响。解剖学上的问题——这些腺体是更像大唾液腺还是小唾液腺——是一个有趣的问题。在与主要腺体共有的特征方面，作者讨论了输卵管腺和舌下腺之间的几个相似之处。例如，输卵管腺缺乏被囊，舌下腺仅部分被囊。作者还在图4中展示了管腺“在咽壁背外侧有多个宏观可见的引流管开口”。舌下腺也通过多种管道分泌其产物。然而，这些特征(纤维囊的缺失和多条导管的存在)与小唾液腺和舌下腺有关，因此可能无法区分大和小的输卵管腺。相反，输卵管腺在几个方面与上颚的小唾液腺相似，这可能暗示了该区域被称为小腺而不是大腺。作者承认这些相似之处，指出“输卵管腺体与腭显微腺体有许多相似之处。”从病理学家的角度来看，无论如何(并基于文本)，输卵管和腭腺的放射学特征之间的关系很难辨别。作者交替地将输卵管腺的PET贪婪度描述为“始终超过上颚的摄取”，和/或“与上颚小唾液腺的粘膜方面和psma配体摄取相当”。这些陈述是否代表了相互矛盾的评估可能超出了我的范围。然而，在解剖学和组织学上，输卵管腺和腭腺之间的共性是显而易见的。例如，图3的显微照片似乎显示腺泡的排列更像小唾液腺。作者还引用了小腺体的分布，而不是大腺体，当讨论历史遗漏/以前无法识别这些腺体。他们的解释是“新发现的输卵管腺涉及扁平的粘膜下腺结构”，这似乎描述了次要唾液单位的形态，而不是主要的腺结构。在某些方面(也许是正确的)，作者削弱了将这些腺体标记为主要和次要的意义。通过写道“我们认为这些鉴定系统可能不适合和不相关地解释和欣赏这一发现”，他们反驳了他们在大部分手稿中强调的适当的输卵管腺名称。通讯作者:Andrew T. Turk，美国纽约哥伦比亚大学欧文医学中心病理与细胞生物学系，e-mail: att2101@cumc.columbia.edu
{"title":"Tubarial or not to be – a potential new organ in the pharynx","authors":"A. Turk","doi":"10.1515/ersc-2020-0002","DOIUrl":"https://doi.org/10.1515/ersc-2020-0002","url":null,"abstract":"In an elegantly presented and thought-provoking manuscript published by the journal Radiotherapy and Oncology, Valstar et al. characterize previously unreported structures comprising salivary gland tissue near the torus tubarius [1]. The authors present their findings in three stages. First, they identify these entities in patients with prostate or urethral gland cancer who underwent positron emission tomography / computed tomography with prostate-specific membrane antigen ligands (PSMA PET/ CT), which technique—despite its name—demonstrates avidity for salivary glands. The investigators then evaluate these glands using human cadavers, and finally assess the effect of radiation therapy involving this region in head & neck cancer (HNC) patients. Ultimately, the authors proffer two conclusions from their findings. First, they propose recognition of this region as newly identified paired organs, suggesting the designation of “tubarial glands.” Second, they underscore the importance of sparing this area from the toxic effects of radiation therapy, to whatever extent feasible. Whereas the second of these points seems more resonant and straightforward, the authors appear to emphasize the first, in terms of coverage and explication. The dichotomy between these claims, and the relative prominence of the purported anatomic contribution within the manuscript, potentially detract from study’s significant clinical impact. The anatomic issue—whether these glands more closely resemble major or minor salivary glands—is an interesting question. In terms of features shared in common with major glands, the authors discuss several analogies between the tubarial glands and sublingual glands. For instance, the tubarial glands lack a capsule, and the sublingual glands show only partial encapsulation. The authors also demonstrate the tubarial glands’ “multiple macroscopically visible draining duct openings in the dorsolateral pharyngeal wall” in Figure 4. The sublingual gland secretes its products through multiple ducts as well. However, these features (absence of a fibrous capsule, and presence of multiple ducts) pertain to minor salivary glands as well as the sublingual gland, and therefore may not distinguish the tubarial glands as major versus minor. Conversely, the tubarial glands exhibit several aspects analogous to the minor salivary glands of the palate, potentially suggesting a designation as minor rather than major glands for the region in question. The authors concede these resemblances, stating “the tubarial glands have many similarities with the palatal conglomerate of microscopic glands.” From the perspective of a pathologist, anyway (and based on the text), the relationship between the radiologic features of the tubarial and palatal glands is difficult to discern. The authors alternately describe the PET avidity of the tubarial glands as “consistently more than the uptake in the palate,” and/or as “comparable to the mucous aspect and PSMA-ligand uptake o","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"3 1","pages":"3 - 4"},"PeriodicalIF":0.7,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79386780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pathology is one of the oldest medical disciplines, one that can be arguably rooted early in Egyptian medicine and Traditional Chinese Medicine 5,000 years ago [1,2]. In ancient times, documentation of diseases relied on the understandings of anatomy and observations of abnormalities that deviated from normal physiology. For many centuries ensued, vast knowledge was accumulated from observations of pathological conditions and autopsies, it is this wealth of information that laid the foundation for the modern medicine we see today. In the early beginning, pathology focused on morphological abnormalities. Random documentation of broken bones, abnormal masses, skin discoloration evolved into systematic gross anatomy in modern pathology in the 19th century [2,3]. The invention of the microscope in the 19th century was undoubtedly another force that propelled pathology and medicine forward, moving us from organbased to cell-based pathology with this “new technology”. Along with the microscope, other technological advances such as tissue fixation, embedding, microtomes, and biological stains, all enabled the practice of histopathology possible. However, for a century, despite the improvement of microscopes and a plethora of ancillary diagnostic tests (i.e. electron microscopy, fluorescent microscopy, immunohistochemistry, cytogenetics), the importance of detecting morphological abnormalities remained constant and central to scientific discoveries, journal publications, and patient care as research focuses moved from organs to cells, from organelles to chromosomes. In recent decades, we have seen an explosion of technologies in science, which enabled comparisons of normal vs. diseased states at molecular levels. Soon, analyses of DNA (single nucleotide polymorphism profiling, whole exome sequencing, cell-free DNA screening, etc.), RNA (RNA-Seq, single cell RNA-Seq, miRNA-Seq, ribosome profiling, etc.), protein (protein microarray, mass spectrometry, quantitative proteomics, etc.), epigenome (ChIPSeq, whole-genome bisulphite sequencing), and metabolome (MS-based metabolites or lipid profiles) at various depths and throughputs became a common practice in experimental approaches and journal publications [4,5]. These molecular analyses not only can identify dysfunctional genes and/or pathways that are responsible or have contributed to the diseased state and structural abnormalities that can be visualized grossly or under a microscope, but may also offer insights for personalized medicine. For instance, in the era of precision medicine for cancer treatment, we have come to recognize that not only there are differential sensitivities to a given therapy among patients, there exists cellular heterogeneity in a patient’s tumor. Therefore, a histological diagnosis of cancer in a patient can be complemented by molecular analyses to devise a personalized therapy that matches the tumor’s molecular profile. It is also the hope that advances in liquid biopsies and ar
病理学是最古老的医学学科之一，可以追溯到5000年前的埃及医学和中医[1,2]。在古代，疾病的记录依赖于对解剖学的理解和对偏离正常生理的异常现象的观察。在接下来的几个世纪里，人们通过观察病理状况和尸检积累了大量的知识，正是这些丰富的信息奠定了我们今天所看到的现代医学的基础。早期病理以形态异常为主。骨折、异常肿块、皮肤变色等随机记录在19世纪的现代病理学中演变为系统的大体解剖学[2,3]。19世纪显微镜的发明无疑是推动病理学和医学向前发展的另一股力量，通过这种“新技术”，我们从以器官为基础的病理学转向了以细胞为基础的病理学。随着显微镜的发展，其他技术的进步，如组织固定、包埋、显微切片和生物染色，都使组织病理学的实践成为可能。然而，一个世纪以来，尽管显微镜和大量辅助诊断测试(如电子显微镜、荧光显微镜、免疫组织化学、细胞遗传学)得到了改进，但随着研究重点从器官转移到细胞、从细胞器转移到染色体，检测形态异常的重要性仍然保持不变，并成为科学发现、期刊出版和患者护理的核心。近几十年来，我们看到了科学技术的爆炸式发展，可以在分子水平上比较正常和患病状态。很快，DNA分析(单核苷酸多态性分析、全外显子组测序、无细胞DNA筛选等)、RNA分析(RNA- seq、单细胞RNA- seq、miRNA-Seq、核糖体分析等)、蛋白质分析(蛋白质微阵列、质谱分析、定量蛋白质组学等)、表观基因组分析(ChIPSeq、全基因组亚硫酸盐测序)、和代谢组(基于质谱的代谢物或脂质谱)在不同深度和通量成为实验方法和期刊出版物中的常见做法[4,5]。这些分子分析不仅可以识别出导致疾病状态和结构异常的功能失调基因和/或途径，这些功能失调基因和/或途径可以在肉眼或显微镜下观察到，而且还可以为个性化医疗提供见解。例如，在癌症治疗的精准医学时代，我们已经认识到，不仅患者对特定疗法的敏感性存在差异，而且患者的肿瘤也存在细胞异质性。因此，癌症患者的组织学诊断可以通过分子分析来补充，从而设计出与肿瘤分子特征相匹配的个性化治疗。人们也希望液体活检和人工智能的进步有一天能取代疾病诊断中组织活检的需要，尽管仍存在许多障碍[6]。细胞病理学可以在细胞、细胞器和分子水平上定义，并且可以通过组织学分析、功能分析或分子分析来检测。基因突变、表观遗传改变或代谢功能障碍都可能导致疾病的发病机制。目前，疾病的诊断通常包括体格检查、大体检查、组织学检查和分子检查。以当前的COVID-19为例，该疾病的出现最初是由于SARS-CoV-2感染患者肺部病理异常而引起的[7]，最终导致了基于pcr的诊断检测的发展。全面开展细胞和分子研究、体外和体内实验、人体和动物研究，共同了解和抗击新冠肺炎。我们认识到细胞的异常状态可以以多方面的方式呈现，因此我们的《细胞病理学》杂志包含了细胞病理学的解剖学、细胞学、分子学、计算学、机械生物学和有机体研究，因为只有通过包括*Gloria H. Su，美国纽约哥伦比亚大学欧文医学中心赫伯特·欧文综合癌症中心耳鼻咽喉头颈外科病理与细胞生物学系，e-mail: gs2157@cumc.columbia.edu
{"title":"Comprehensive outlook of Cell Pathology","authors":"G. Su","doi":"10.1515/ersc-2020-0001","DOIUrl":"https://doi.org/10.1515/ersc-2020-0001","url":null,"abstract":"Pathology is one of the oldest medical disciplines, one that can be arguably rooted early in Egyptian medicine and Traditional Chinese Medicine 5,000 years ago [1,2]. In ancient times, documentation of diseases relied on the understandings of anatomy and observations of abnormalities that deviated from normal physiology. For many centuries ensued, vast knowledge was accumulated from observations of pathological conditions and autopsies, it is this wealth of information that laid the foundation for the modern medicine we see today. In the early beginning, pathology focused on morphological abnormalities. Random documentation of broken bones, abnormal masses, skin discoloration evolved into systematic gross anatomy in modern pathology in the 19th century [2,3]. The invention of the microscope in the 19th century was undoubtedly another force that propelled pathology and medicine forward, moving us from organbased to cell-based pathology with this “new technology”. Along with the microscope, other technological advances such as tissue fixation, embedding, microtomes, and biological stains, all enabled the practice of histopathology possible. However, for a century, despite the improvement of microscopes and a plethora of ancillary diagnostic tests (i.e. electron microscopy, fluorescent microscopy, immunohistochemistry, cytogenetics), the importance of detecting morphological abnormalities remained constant and central to scientific discoveries, journal publications, and patient care as research focuses moved from organs to cells, from organelles to chromosomes. In recent decades, we have seen an explosion of technologies in science, which enabled comparisons of normal vs. diseased states at molecular levels. Soon, analyses of DNA (single nucleotide polymorphism profiling, whole exome sequencing, cell-free DNA screening, etc.), RNA (RNA-Seq, single cell RNA-Seq, miRNA-Seq, ribosome profiling, etc.), protein (protein microarray, mass spectrometry, quantitative proteomics, etc.), epigenome (ChIPSeq, whole-genome bisulphite sequencing), and metabolome (MS-based metabolites or lipid profiles) at various depths and throughputs became a common practice in experimental approaches and journal publications [4,5]. These molecular analyses not only can identify dysfunctional genes and/or pathways that are responsible or have contributed to the diseased state and structural abnormalities that can be visualized grossly or under a microscope, but may also offer insights for personalized medicine. For instance, in the era of precision medicine for cancer treatment, we have come to recognize that not only there are differential sensitivities to a given therapy among patients, there exists cellular heterogeneity in a patient’s tumor. Therefore, a histological diagnosis of cancer in a patient can be complemented by molecular analyses to devise a personalized therapy that matches the tumor’s molecular profile. It is also the hope that advances in liquid biopsies and ar","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"65 1","pages":"1 - 2"},"PeriodicalIF":0.7,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83747035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Cystic fibrosis (CF) is a life-shortening, genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The primary cause of CF is reduced CFTR-mediated chloride and bicarbonate transport, due to mutations in CFTR. However, inflammation and persistent infections influence clinical outcome. Cellular stress response pathways, such as the unfolded protein response (UPR) and the integrated stress response (ISR), referred to here as cellular stress response pathways (SRPs), contribute to the pathology of human disorders. Multiple studies have indicated activation of SRPs in CF tissues. We review our present understanding of how SRPs are activated in CF and their contribution to pathology. We conclude that reduced CFTR function in CF organs establishes a tissue environment in which internal or external insults activate SRPs. SRPs contribute to CF pathogenesis by reducing CFTR expression, enhancing inflammation with consequent tissue remodeling. Understanding the contribution of SRPs to CF pathogenesis is crucial even in the era of CFTR “modulators” that are designed to potentiate, correct or amplify CFTR function, since there is an urgent need for supportive treatments. Importantly, CF patients with established pathology could benefit from the targeted use of drugs that modulate SRPs to reduce the symptoms.
{"title":"Stressors and Stress Responses in Cystic Fibrosis","authors":"Z. Bebok, Lianwu Fu","doi":"10.1515/ersc-2018-0002","DOIUrl":"https://doi.org/10.1515/ersc-2018-0002","url":null,"abstract":"Abstract Cystic fibrosis (CF) is a life-shortening, genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The primary cause of CF is reduced CFTR-mediated chloride and bicarbonate transport, due to mutations in CFTR. However, inflammation and persistent infections influence clinical outcome. Cellular stress response pathways, such as the unfolded protein response (UPR) and the integrated stress response (ISR), referred to here as cellular stress response pathways (SRPs), contribute to the pathology of human disorders. Multiple studies have indicated activation of SRPs in CF tissues. We review our present understanding of how SRPs are activated in CF and their contribution to pathology. We conclude that reduced CFTR function in CF organs establishes a tissue environment in which internal or external insults activate SRPs. SRPs contribute to CF pathogenesis by reducing CFTR expression, enhancing inflammation with consequent tissue remodeling. Understanding the contribution of SRPs to CF pathogenesis is crucial even in the era of CFTR “modulators” that are designed to potentiate, correct or amplify CFTR function, since there is an urgent need for supportive treatments. Importantly, CF patients with established pathology could benefit from the targeted use of drugs that modulate SRPs to reduce the symptoms.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"8 1","pages":"11 - 29"},"PeriodicalIF":0.7,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84782155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Ire1 and its family protein PERK are endoplasmic reticulum (ER)-stress sensors that initiate cellular responses against ER accumulation of unfolded proteins. As reviewed in this article, many publications describe molecular mechanisms by which yeast Ire1 senses ER conditions and gets regulated. We also cover recent studies which reveal that mammalian Ire1 (IRE1α) and PERK are controlled in a similar but not exactly the same manner. ER-located molecular chaperone BiP captures these ER-stress sensors and suppresses their activity. Intriguingly, Ire1 is associated with BiP not as a chaperone substrate, but as a unique ligand. Unfolded proteins accumulated in the ER promote dissociation of the Ire1-BiP complex. Moreover, Ire1 is directly bound with unfolded proteins, leading to its cluster formation and potent activation. PERK also captures unfolded proteins and then forms self-oligomers. Meanwhile, membrane-lipid aberrancy is likely to activate these ER-stress sensors independently of ER accumulation of unfolded proteins. In addition, there exist a number of reports that touch on other factors that control activity of these ER-stress sensors. Such a multiplicity of regulatory mechanisms for these ER-stress sensors is likely to contribute to fine tuning of their activity.
{"title":"Stress-sensing and regulatory mechanism of the endoplasmic-stress sensors Ire1 and PERK","authors":"Yuki Ishiwata‐Kimata, G. Q. Le, Y. Kimata","doi":"10.1515/ersc-2018-0001","DOIUrl":"https://doi.org/10.1515/ersc-2018-0001","url":null,"abstract":"Abstract Ire1 and its family protein PERK are endoplasmic reticulum (ER)-stress sensors that initiate cellular responses against ER accumulation of unfolded proteins. As reviewed in this article, many publications describe molecular mechanisms by which yeast Ire1 senses ER conditions and gets regulated. We also cover recent studies which reveal that mammalian Ire1 (IRE1α) and PERK are controlled in a similar but not exactly the same manner. ER-located molecular chaperone BiP captures these ER-stress sensors and suppresses their activity. Intriguingly, Ire1 is associated with BiP not as a chaperone substrate, but as a unique ligand. Unfolded proteins accumulated in the ER promote dissociation of the Ire1-BiP complex. Moreover, Ire1 is directly bound with unfolded proteins, leading to its cluster formation and potent activation. PERK also captures unfolded proteins and then forms self-oligomers. Meanwhile, membrane-lipid aberrancy is likely to activate these ER-stress sensors independently of ER accumulation of unfolded proteins. In addition, there exist a number of reports that touch on other factors that control activity of these ER-stress sensors. Such a multiplicity of regulatory mechanisms for these ER-stress sensors is likely to contribute to fine tuning of their activity.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"119 1","pages":"1 - 10"},"PeriodicalIF":0.7,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87753985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toru Hosoi, J. Nomura, Keigo Tanaka, K. Ozawa, A. Nishi, Y. Nomura
Abstract Increasing evidence suggests that endoplasmic reticulum (ER) stress and autophagy play an important role in regulating brain function. ER stress activates three major branches of the unfolded protein response (UPR) pathways, namely inositol-requiring enzyme-1 (IRE1), double stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK) and activating transcription factor 6 (ATF6)-mediated pathways. Recent studies have suggested that these UPR signals may be linked to autophagy. In this review article, we summarize recent evidence and discuss a possible link between ER stress and autophagy with regard to neurodegenerative diseases. Furthermore, possible pharmacological strategies targeting UPR and autophagy are discussed.
{"title":"Link between endoplasmic reticulum stress and autophagy in neurodegenerative diseases","authors":"Toru Hosoi, J. Nomura, Keigo Tanaka, K. Ozawa, A. Nishi, Y. Nomura","doi":"10.1515/ersc-2017-0004","DOIUrl":"https://doi.org/10.1515/ersc-2017-0004","url":null,"abstract":"Abstract Increasing evidence suggests that endoplasmic reticulum (ER) stress and autophagy play an important role in regulating brain function. ER stress activates three major branches of the unfolded protein response (UPR) pathways, namely inositol-requiring enzyme-1 (IRE1), double stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK) and activating transcription factor 6 (ATF6)-mediated pathways. Recent studies have suggested that these UPR signals may be linked to autophagy. In this review article, we summarize recent evidence and discuss a possible link between ER stress and autophagy with regard to neurodegenerative diseases. Furthermore, possible pharmacological strategies targeting UPR and autophagy are discussed.","PeriodicalId":29730,"journal":{"name":"Cell Pathology","volume":"46 1","pages":"37 - 45"},"PeriodicalIF":0.7,"publicationDate":"2017-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78075040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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