{"title":"Interferon Gamma: Influence on Neural Stem Cell Function in Neurodegenerative and Neuroinflammatory Disease","authors":"Apurva Kulkarni, P. Ganesan, Lauren A. O'Donnell","doi":"10.4137/CPath.S40497","DOIUrl":"https://doi.org/10.4137/CPath.S40497","url":null,"abstract":"Interferon-gamma (IFNγ), a pleiotropic cytokine, is expressed in diverse neurodegenerative and neuroinflammatory conditions. Its protective mechanisms are well documented during viral infections in the brain, where IFNγ mediates non-cytolytic viral control in infected neurons. However, IFNγ also plays both protective and pathological roles in other central nervous system (CNS) diseases. Of the many neural cells that respond to IFNγ, neural stem/progenitor cells (NSPCs), the only pluripotent cells in the developing and adult brain, are often altered during CNS insults. Recent studies highlight the complex effects of IFNγ on NSPC activity in neurodegenerative diseases. However, the mechanisms that mediate these effects, and the eventual outcomes for the host, are still being explored. Here, we review the effects of IFNγ on NSPC activity during different pathological insults. An improved understanding of the role of IFNγ would provide insight into the impact of immune responses on the progression and resolution of neurodegenerative diseases.","PeriodicalId":43543,"journal":{"name":"Clinical Medicine Insights- Pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82279540","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}
J. A. Lorentzen, K. Grzyb, P. D. De Angelis, G. Hoff, T. Eide, P. A. Andresen
{"title":"Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study","authors":"J. A. Lorentzen, K. Grzyb, P. D. De Angelis, G. Hoff, T. Eide, P. A. Andresen","doi":"10.4137/CPath.S40143","DOIUrl":"https://doi.org/10.4137/CPath.S40143","url":null,"abstract":"Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.0% of the lesions and were significantly associated with tubulovillous adenomas and large size. A significantly higher frequency of KRAS mutations in females was associated with mutations in codon 12. The KRAS exon 3 and 4 mutations constituted 23.4% of the KRAS positive lesions, which is a larger proportion compared to previous observations in colorectal cancer. BRAF mutations were identified in 11.3% and were associated with serrated polyps. None of the individuals were diagnosed with de novo or recurrent colorectal cancer during the follow-up time (median 11.2 years). Revealing differences in mutation-spectra according to gender and stages in tumorigenesis might be important for optimal use of oncogenes as therapeutic targets and biomarkers.","PeriodicalId":43543,"journal":{"name":"Clinical Medicine Insights- Pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89726998","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}
{"title":"Sudden Cardiac Death of a Body Packer Due to Cocaine Cardiotoxicity","authors":"P. Pramanik, R. Vidua","doi":"10.4137/CPath.S41070","DOIUrl":"https://doi.org/10.4137/CPath.S41070","url":null,"abstract":"This article presents a case of sudden cardiac death due to the effects of cocaine concealed in the body of a male drug smuggler in his 40s, a so-called body packer. A total of 57 body packets filled with cocaine powder were discovered in his body cavities. The detailed autopsy examination, including histopathology and toxicology findings, is discussed with the aim of describing the mechanism of cocaine intoxication in the body packer and an analysis of cocaine-induced cardiotoxicity and sudden death.","PeriodicalId":43543,"journal":{"name":"Clinical Medicine Insights- Pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85844796","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}
Andresa Borges Soares, Albina Altemani, Thais Ribeiro de Oliveira, Felipe de Oliveira Fonseca Rodrigues, Alfredo Ribeiro-Silva, Danilo Figueiredo Soave, Fabricio Passador-Santos, Suellen Trentin Brum, Marcelo Henrique Napimoga, Vera Cavalcanti de Araújo
{"title":"Comparison of the blood and lymphatic microvessel density of pleomorphic adenoma and Basal cell adenoma.","authors":"Andresa Borges Soares, Albina Altemani, Thais Ribeiro de Oliveira, Felipe de Oliveira Fonseca Rodrigues, Alfredo Ribeiro-Silva, Danilo Figueiredo Soave, Fabricio Passador-Santos, Suellen Trentin Brum, Marcelo Henrique Napimoga, Vera Cavalcanti de Araújo","doi":"10.4137/CPath.S23035","DOIUrl":"https://doi.org/10.4137/CPath.S23035","url":null,"abstract":"<p><strong>Background: </strong>Pleomorphic adenoma (PA) is the most common tumor of the salivary gland, while basal cell adenoma (BCA) is an uncommon neoplasm. Blood and lymphatic vessels are crucial for tumor metabolism. The aim of this study was to compare the blood and lymphatic vascular density and vascular and endothelial growth factor (VEGF) expression in PA and BCA tumors. In addition, cell proliferation was evaluated in these tumors.</p><p><strong>Methods: </strong>Blood and lymphatic vessel content, VEGF expression, and cell proliferation were analyzed in 30 cases of PA and 13 cases of BCA by immu-nohistochemistry using antibodies for CD34, CD105, D2-40, VEGF, and Mcm-2.</p><p><strong>Results: </strong>Regarding CD34 and CD105 expression, PA demonstrated a high vascularity and a low number of positive vessels, respectively. D2-40-positive lymphatic vessels were mainly located in the tumor capsules, with small intratumoral lymphatic vessels observed occasionally. VEGF expression revealed a remarkably heterogeneous immunoreactivity, alternating from weak or negative to positive or intense. BCA presented significantly higher CD34, CD34, CD105, D2-40, and VEGF expression compared to PA. No significant difference was found in cell proliferation between the tumors.</p><p><strong>Conclusion: </strong>Although PA and BCA are considered part of the same spectrum of differentiation, this study showed that the blood and lymphatic vascularization of these tumors is different.</p>","PeriodicalId":43543,"journal":{"name":"Clinical Medicine Insights- Pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/CPath.S23035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33316035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jaafar Makki, Ohnmar Myint, Aye Aye Wynn, Ahmad Toha Samsudin, Daisy Vanitha John
{"title":"Expression distribution of cancer stem cells, epithelial to mesenchymal transition, and telomerase activity in breast cancer and their association with clinicopathologic characteristics.","authors":"Jaafar Makki, Ohnmar Myint, Aye Aye Wynn, Ahmad Toha Samsudin, Daisy Vanitha John","doi":"10.4137/CPath.S19615","DOIUrl":"https://doi.org/10.4137/CPath.S19615","url":null,"abstract":"<p><p>A total of 167 surgically resected primary invasive breast carcinomas and 63 metastatic lymph node lesions were analyzed for immunohistochemical (IHC) localization of the CD44(+)CD24(-low) breast cancer stem cell (CSC) markers, epithelial to mesenchymal transition (EMT) markers, and telomerase activity by double-staining IHC technique, in formalin-fixed, paraffin-embedded tissue, the results were validated by double-staining immunofluorescent and flow cytometry techniques. The results showed that CSCs with CD44(+)CD24(-low) phenotype were significantly increased in node-positive tumors, high-grade tumors, and ductal carcinoma in situ (DCIS). There was a high incidence of telomerase expression in metastatic lymph node lesion. There were considerably high number of tumor cells with EMT expression in metastatic lymph node lesion, and triple-negative tumor. The occurrence of EMT phenomena was usually accompanied by the co-existence of CSCs of CD44(+)CD24(-low) phenotype. There was no association between the existence of CSCs and detection of telomerase activity in tumor cells. Increased numbers of both CSCs of CD44(+)CD24(-low) phenotype and cells underwent EMT in DCIS lesion might be an initial step in the stromal invasion and propagation of breast cancer, and occurrence of EMT in the breast tumor associated with high prevalence of CSCs, promoting tumor invasiveness and metastasis. </p>","PeriodicalId":43543,"journal":{"name":"Clinical Medicine Insights- Pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/CPath.S19615","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33330892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance","authors":"J. Makki","doi":"10.4137/CPath.S31563","DOIUrl":"https://doi.org/10.4137/CPath.S31563","url":null,"abstract":"Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality, with an incidence of ≥1,000,000 cases occurring worldwide annually. It is one of the most common human neoplasms, accounting for approximately one-quarter of all cancers in females worldwide and 27% of cancers in developed countries with a Western lifestyle. They exhibit a wide scope of morphological features, different immunohistochemical profiles, and unique histopathological subtypes that have specific clinical course and outcome. Breast cancers can be classified into distinct subgroups based on similarities in the gene expression profiles and molecular classification.","PeriodicalId":43543,"journal":{"name":"Clinical Medicine Insights- Pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88129876","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}
{"title":"Chronic Lymphocytic Leukemia with t(14;18)(q32;q21) As a Sole Cytogenetic Abnormality.","authors":"Ghaleb Elyamany, Kamal Fadalla, Hatem Elghezal, Omar Alsuhaibani, Hani Osman, Abdulaziz Al-Abulaaly","doi":"10.4137/CPath.S17818","DOIUrl":"https://doi.org/10.4137/CPath.S17818","url":null,"abstract":"<p><strong>Background: </strong>Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. The chromosomal abnormality t(14;18)(q32;q21) is most commonly associated with neoplasms of a follicular center cell origin. However, t(14;18) has also been reported in rare cases of CLL.</p><p><strong>Objective: </strong>We describe the clinicopathologic, immunophenotypic, conventional, and molecular cytogenetic features of two rare cases proven to be CLL morphologically and immunologically in which t(14;18) was found as the sole cytogenetic abnormality.</p><p><strong>Methods: </strong>Morphologic, flow cytometric analysis and molecular cytogenetic of peripheral blood and/or bone marrow samples were analyzed.</p><p><strong>Results: </strong>Cytomorphologically, the cells were small mature lymphocytes without any findings that had characteristics of follicular lymphoma (FL) such as indented or clefted nuclei. Immunologic findings were characteristic of typical CLL without expression of CD10. A cytogenetic study revealed the two cases of CLL carrying t(14;18)(q32;q21).</p><p><strong>Conclusion: </strong>We concluded that CLL with t(14;18) is rare and should be differentiated from FL as the therapy is highly diverse between both diseases. Using immunoglobulin heavy chain gene (IGH) probes are important in the workup of patients with suspected CLL and suggest that the IGH probe should be used routinely in all CLL fluorescence in situ hybridization (FISH) panels.</p>","PeriodicalId":43543,"journal":{"name":"Clinical Medicine Insights- Pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/CPath.S17818","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32725416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer L Quon, Ryan A Grant, Anita J Huttner, Charles C Duncan
{"title":"Thoracic epidural teratoma: case report and review of the literature.","authors":"Jennifer L Quon, Ryan A Grant, Anita J Huttner, Charles C Duncan","doi":"10.4137/CPath.S14723","DOIUrl":"https://doi.org/10.4137/CPath.S14723","url":null,"abstract":"<p><strong>Purpose: </strong>Spinal teratomas comprise a rare subset of spinal cord tumors, and here, we describe an even rarer childhood thoracic extradural-intracanalicular teratoma. The clinical presentation, management, and pathophysiology of these tumors are reviewed to promote recognition and guide treatment of these lesions.</p><p><strong>Methods: </strong>We report the case of a 21-month-old boy who presented with marked spasticity, as well as failure to ambulate and meet motor milestones. Additionally, we provide a literature review of spinal teratomas, including their clinical presentation, work-up, pathophysiology, and underlying genetics.</p><p><strong>Results: </strong>An MRI of the spine revealed a large dorsal epidural tumor extending from T3 to T10 with heterogeneous contrast enhancement and severe spinal cord compression. The tumor was resected revealing a cystic mass with tissue resembling hair, muscle, as well as cartilage; pathology confirmed the diagnosis of teratoma. Gross total resection was achieved, and the child eventually gained ambulatory function.</p><p><strong>Conclusions: </strong>Given that spinal teratomas are rare entities that can present with significant neurologic compromise, they must remain on clinicians' differentials. Unfortunately, the exact origin of these tumors remains inconclusive and requires further investigation.</p>","PeriodicalId":43543,"journal":{"name":"Clinical Medicine Insights- Pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/CPath.S14723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32432546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victor C Kok, Chien-Kuan Lee, Jorng-Tzong Horng, Che-Chen Lin, Fung-Chang Sung
{"title":"Reappraisal of the etiology of extracorpuscular non-autoimmune acquired hemolytic anemia in 2657 hospitalized patients with non-neoplastic disease.","authors":"Victor C Kok, Chien-Kuan Lee, Jorng-Tzong Horng, Che-Chen Lin, Fung-Chang Sung","doi":"10.4137/CPath.S14875","DOIUrl":"https://doi.org/10.4137/CPath.S14875","url":null,"abstract":"<p><strong>Introduction: </strong>Unlike autoimmune hemolytic anemia (AIHA), literature on the etiological study of non-autoimmune hemolytic anemia (non-AIHA) is scarce. The incidence and prevalence of non-AIHA in different geographic regions are largely unknown perhaps owing to the lack of perspective investigation and different profiles of etiologies from different geographic regions. We aimed to examine the real-world etiology or mechanisms of the non-hereditary non-AIHA from a nationwide population-based administrative claim database in Taiwan.</p><p><strong>Patients and methods: </strong>The National Health Insurance Research Database of Taiwan was adopted for this research. The studied population was total inpatient claim records including both pediatric and adult patients, contributed by a population of 23 million insured individuals in Taiwan. From 2002 to 2008, we retrieved 3,903 patients having no pre-existing malignancy discharged after inpatient management for acquired hemolytic anemia, which was defined as coding in discharge diagnoses containing ICD-9-CM code 283. By contrast, ICD-9-CM code 282 and all of the sub-codes are for hereditary hemolytic anemias.</p><p><strong>Results: </strong>AIHA accounted for 32% of the total cases. Among 2,657 patients with non-AIHA, mechanical or microangiopathic mechanism accounted for 19% of cases; hemolytic-uremic syndrome (HUS) 4%, hemoglobinuria because of hemolysis from external causes such as paroxysmal nocturnal hemoglobinuria (PNH) and march hemoglobinuria 7%, and chronic idiopathic hemolytic anemia or other unspecified non-AIHA 69%. We looked further for specific etiology or mechanism for this group of patients with non-hereditary extrinsic non-AIHA (n = 2,657). The explanatory disease states or conditions were splenomegaly; alcohol use disorder (spur cell hemolysis); heart-valve prosthesis; malignant hypertension; disseminated intravascular coagulation; transfusion reaction; dengue fever-induced hemolytic anemia; direct parasitization; snake, lizard, or spider bite; and Wilson's disease with internal toxin mechanism. All these cases can explain up to 34.6% of all the non-hereditary extrinsic non-AIHA cases. Fragmentation hemolysis (HUS, heart-valve prosthesis, malignant hypertension, and disseminated intravascular coagulation) accounted for 7.4% of non-AIHA hospitalized patients with non-neoplastic disease.</p><p><strong>Conclusions: </strong>This article is the first one to clearly demonstrate that the non-neoplastic-induced HUS requiring hospitalization cases in Taiwan, which has a population of over 23 million were 110 over a span of seven years, 16 cases per year. Although the etiologies of non-AIHA are well known and described in the literature, this work added the statistical percentages of the various etiologies of non-AIHA in Taiwan.</p>","PeriodicalId":43543,"journal":{"name":"Clinical Medicine Insights- Pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/CPath.S14875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32326238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular insights into systemic lupus erythematosus pathogenesis.","authors":"Dama Laxminarayana","doi":"10.4137/CPath.S14814","DOIUrl":"https://doi.org/10.4137/CPath.S14814","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a complex, heterogeneous, and chronic autoimmune disorder of an unknown origin. Its clinical symptoms range from a benign skin disorder to severe, life-threatening conditions.1 Immune effector dysfunctions are hall marks of SLE disease.2 The etiopathogenesis of the altered immune response in SLE remains unknown. SLE is characterized by the presence of auto-antibodies (AutoAbs) for a wide variety of self antigens and circulating immune complexes.1,2 The onset of lupus is variable and may affect all stages of life. The disease predominantly affiicts females in the child-bearing years about 6- to 10-fold more frequently than males. We have not had a new drug in 50 years, because of the unknown etiology of the abnormal immune response. The current lupus therapies are non-specific, symptomatic, and cause significant side effects. In this editorial, I have made an attempt to describe multistep immune alterations that pave the way for the inception and sustaining of SLE pathogenesis, and postulated molecular mechanisms involved in SLE disease onset. Such information will help in better understanding SLE etiopathogenesis and in developing effective and safer strategies to combat SLE as well as other autoimmune diseases.","PeriodicalId":43543,"journal":{"name":"Clinical Medicine Insights- Pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/CPath.S14814","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32216757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}