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Neuro-oncology Aug 2021The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the... (Review)
Review
The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.
Topics: Brain; Central Nervous System; Central Nervous System Neoplasms; Humans; Pathology, Molecular; World Health Organization
PubMed: 34185076
DOI: 10.1093/neuonc/noab106 -
International Journal of Molecular... Sep 2023Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by... (Review)
Review
Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by changes in bone homeostasis, which lead to reduced bone mass, impaired bone quality, and an increased risk of fractures. The pathophysiology of osteoporosis is complex and multifactorial, involving imbalances in hormones, cytokines, and growth factors. Understanding the cellular and molecular mechanisms underlying osteoporosis is essential for appropriate diagnosis and management of the condition. This paper provides a comprehensive review of the normal cellular and molecular mechanisms of bone homeostasis, followed by an in-depth discussion of the proposed pathophysiology of osteoporosis through the osteoimmunological, gut microbiome, and cellular senescence models. Furthermore, the diagnostic tools used to assess osteoporosis, including bone mineral density measurements, biochemical markers of bone turnover, and diagnostic imaging modalities, are also discussed. Finally, both the current pharmacological and non-pharmacological treatment algorithms and management options for osteoporosis, including an exploration of the management of osteoporotic fragility fractures, are highlighted. This review reveals the need for further research to fully elucidate the molecular mechanisms underlying the condition and to develop more effective therapeutic strategies.
Topics: Humans; Pathology, Molecular; Osteoporosis; Osteoporotic Fractures; Bone Density; Bone and Bones
PubMed: 37834025
DOI: 10.3390/ijms241914583 -
Surgical Pathology Clinics Sep 2021The identification of targetable genomic alterations in lung cancer is required as standard of care to guide optimal therapy selection. With a constantly evolving... (Review)
Review
The identification of targetable genomic alterations in lung cancer is required as standard of care to guide optimal therapy selection. With a constantly evolving landscape of ancillary molecular and biomarker testing in lung cancer, pathologists need to be aware of what specimens to test, how the testing should be performed, and which targets to test for to provide the clinically relevant genomic information necessary to treat these patients. Several guideline statements on the topic are currently available to help pathologists and laboratory personnel best use the small specimens obtained from patients with lung cancer for ancillary molecular testing.
Topics: Biomarkers, Tumor; Genomics; Humans; Lung Neoplasms; Pathologists; Pathology, Molecular
PubMed: 34373089
DOI: 10.1016/j.path.2021.05.002 -
Journal of Clinical Microbiology Oct 2022Nearly 40 years have elapsed since the invention of the PCR, with its extremely sensitive and specific ability to detect nucleic acids via enzyme-mediated... (Review)
Review
Nearly 40 years have elapsed since the invention of the PCR, with its extremely sensitive and specific ability to detect nucleic acids via enzyme-mediated amplification. In turn, more than 2 years have passed since the onset of the coronavirus disease 2019 (COVID-19) pandemic, during which time molecular diagnostics for infectious diseases have assumed a larger global role than ever before. In this context, we review broadly the progression of molecular techniques in clinical microbiology, to their current prominence. Notably, these methods now entail both the detection and quantification of microbial nucleic acids, along with their sequence-based characterization. Overall, we seek to provide a combined perspective on the techniques themselves, as well as how they have come to shape health care at the intersection of technologic innovation, pathophysiologic knowledge, clinical/laboratory logistics, and even financial/regulatory factors.
Topics: Humans; Pathology, Molecular; COVID-19; Nucleic Acid Amplification Techniques; Communicable Diseases; Nucleic Acids; Molecular Diagnostic Techniques
PubMed: 35852340
DOI: 10.1128/jcm.02446-21 -
Human Pathology Jan 2020The past 50 years has been an era of technological innovation converging with the now dominant culture of testing hypotheses using clinical trials and case cohort... (Review)
Review
The past 50 years has been an era of technological innovation converging with the now dominant culture of testing hypotheses using clinical trials and case cohort methodology with rigorous statistical analysis. Great advances have been made in early diagnosis and, especially, less toxic and disfiguring primary therapy. Many of the advances in pathology have been in conjunction with efforts to support clinical initiatives, improve diagnostic reliability and translate basic science discoveries into tests that stratify patient management. Pathologists, with the support of epidemiologists, have lead significant advancements in the description and clinical significance of benign breast disease. Despite considerable efforts, the cure for breast cancer awaits better understanding of the pathophysiology of metastasis. We stand now at the brink a new era of technology, in which powerful genomic assays may be put to use in uncovering targets of therapy and defining mechanisms of disease progression. Pathologists must be active in ensuring that discoveries in this realm are optimized by assuring association with appropriate histological correlation and valid clinical endpoints.
Topics: Biomarkers, Tumor; Breast; Breast Neoplasms; Diffusion of Innovation; Female; Genetic Predisposition to Disease; History, 20th Century; History, 21st Century; Humans; Pathology, Molecular
PubMed: 31682887
DOI: 10.1016/j.humpath.2019.09.007 -
The Journal of Molecular Diagnostics :... Sep 2023The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of... (Review)
Review
CYP3A4 and CYP3A5 Genotyping Recommendations: A Joint Consensus Recommendation of the Association for Molecular Pathology, Clinical Pharmacogenetics Implementation Consortium, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, European...
The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations for a minimum panel of variant alleles (tier 1) and an extended panel of variant alleles (tier 2) that will aid clinical laboratories when designing assays for PGx testing. The Association for Molecular Pathology PGx Working Group considered functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. The goal of this Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. This document will focus on clinical CYP3A4 and CYP3A5 PGx testing that may be applied to all CYP3A4- and CYP3A5-related medications. These recommendations are not to be interpreted as prescriptive but to provide a reference guide.
Topics: Humans; Pharmacogenetics; Cytochrome P-450 CYP3A; Genotype; Consensus; Pathology, Molecular; Pharmacists; Pathologists
PubMed: 37419245
DOI: 10.1016/j.jmoldx.2023.06.008 -
International Journal of Molecular... Mar 2023Although the incidence of sarcomas accounts for less than 1% of all malignancies, they are classified into more than 50 different subtypes with different biological...
Although the incidence of sarcomas accounts for less than 1% of all malignancies, they are classified into more than 50 different subtypes with different biological behaviours [...].
Topics: Humans; Pathology, Molecular; Sarcoma; Incidence; Soft Tissue Neoplasms
PubMed: 36982907
DOI: 10.3390/ijms24065833 -
International Journal of Molecular... Dec 2022Years of standing still have ended, and the field of nephrology has seen a plethora of clinical trials, changing the therapeutic landscape of chronic kidney disease...
Years of standing still have ended, and the field of nephrology has seen a plethora of clinical trials, changing the therapeutic landscape of chronic kidney disease (CKD) and immune-mediated kidney disease management [...].
Topics: Humans; Pathology, Molecular; Kidney; Renal Insufficiency, Chronic; Nephrology
PubMed: 36555648
DOI: 10.3390/ijms232416006 -
Journal of Experimental & Clinical... Jun 2020Accumulating evidence indicates that intratumoral heterogeneity contributes to the development of resistance to anticancer therapeutics. Fibroblasts, which are... (Review)
Review
Accumulating evidence indicates that intratumoral heterogeneity contributes to the development of resistance to anticancer therapeutics. Fibroblasts, which are components of the paraneoplastic stroma, play a crucial role in the wound-healing process. Activated fibroblasts accumulate in the wound and are involved in many aspects of the tissue remodeling cascade that initiates the repair process and prevents further tissue damage. The pathophysiological roles of cancer-associated fibroblasts (CAFs) in the heterogeneous tumor microenvironment have attracted increasing interest. CAFs play crucial roles in tumor progression and the response to chemotherapy. Several cytokines and chemokines are involved in the conversion of normal fibroblasts into CAFs, and some of these form a feedback loop between cancer cells and CAFs. In addition, the physical force between tumor cells and CAFs promotes cooperative invasion or co-migration of both types of cells. Pro-inflammatory cytokines, such as leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), are secreted by both cancer cells and CAFs, and mediate the epigenetic modification of CAFs. This enhances the pro-tumorigenic function of CAFs mediated by promoting actomyosin contractility and extracellular matrix remodeling to form the tracks used for collective cancer cell migration. The concept of intra-tumoral CAF heterogeneity refers to the presence of inflammatory CAFs with low levels of α-smooth muscle actin (α-SMA) and high levels of IL-6 expression, which are in striking contrast to transforming growth factor-β (TGF-β)-dependent myofibroblastic CAFs with high α-SMA expression levels. CAF populations that suppress tumor growth and progression through stroma-specific Hedgehog (Hh) activation have been detected in different murine tumor models including those of the bladder, colon, and pancreas. A new therapeutic strategy targeting CAFs is the "stromal switch," in which tumor-promoting CAFs are changed into tumor-retarding CAFs with attenuated stromal stiffness. Several molecular mechanisms that can be exploited to design personalized anticancer therapies targeting CAFs remain to be elucidated. Strategies aimed at targeting the tumor stroma as well as tumor cells themselves have attracted academic attention for their application in precision medicine. This novel review discusses the role of the activation of EGFR, Wnt/β-catenin, Hippo, TGF-β, and JAK/STAT cascades in CAFs in relation to the chemoresistance and invasive/metastatic behavior of cancer cells. For instance, although activated EGFR signaling contributes to collective cell migration in cooperation with CAFs, an activated Hippo pathway is responsible for stromal stiffness resulting in the collapse of neoplastic blood vessels. Therefore, identifying the signaling pathways that are activated under specific conditions is crucial for precision medicine.
Topics: Animals; Cancer-Associated Fibroblasts; Humans; Neoplasms; Pathology, Molecular; Signal Transduction
PubMed: 32546182
DOI: 10.1186/s13046-020-01611-0 -
Diagnostic Cytopathology Jan 2023In the era of personalized medicine, molecular testing plays a critical role in patient care. The rapid advance of molecular techniques, especially next-generation...
In the era of personalized medicine, molecular testing plays a critical role in patient care. The rapid advance of molecular techniques, especially next-generation sequencing, makes molecular diagnosis feasible in daily practice. Molecular testing can be used as a valuable ancillary test to increase diagnostic sensitivity and specificity, especially in small biopsy or cytology samples. In addition, molecular testing plays an important role in selecting patients for appropriate treatment by detecting therapeutic and predictive biomarkers in tissue or cytology samples. Molecular studies can be applied in all cytology samples, sometimes with better results than histology. As molecular testing has become essential for patient care and is often requested to be performed in cytology samples, it is critical for cytopathologists to understand the basics of molecular diagnostic methods, indications for molecular testing, and how to best utilize different cytologic samples for this purpose. In this special issue, experts in various areas of cytopathology and molecular pathology review the literature and discuss the basics of molecular techniques and the application of molecular testing in various types of cytology samples. It is our hope that after reading the articles in this special issue, the readers can know better about the possibilities of molecular cytology, a very exciting field of pathology.
Topics: Humans; Pathology, Molecular; Molecular Diagnostic Techniques
PubMed: 36367273
DOI: 10.1002/dc.25071