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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 -
The Journal of Molecular Diagnostics :... May 2017Next-generation sequencing (NGS) methods for cancer testing have been rapidly adopted by clinical laboratories. To establish analytical validation best practice... (Review)
Review
Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists.
Next-generation sequencing (NGS) methods for cancer testing have been rapidly adopted by clinical laboratories. To establish analytical validation best practice guidelines for NGS gene panel testing of somatic variants, a working group was convened by the Association of Molecular Pathology with liaison representation from the College of American Pathologists. These joint consensus recommendations address NGS test development, optimization, and validation, including recommendations on panel content selection and rationale for optimization and familiarization phase conducted before test validation; utilization of reference cell lines and reference materials for evaluation of assay performance; determining of positive percentage agreement and positive predictive value for each variant type; and requirements for minimal depth of coverage and minimum number of samples that should be used to establish test performance characteristics. The recommendations emphasize the role of laboratory director in using an error-based approach that identifies potential sources of errors that may occur throughout the analytical process and addressing these potential errors through test design, method validation, or quality controls so that no harm comes to the patient. The recommendations contained herein are intended to assist clinical laboratories with the validation and ongoing monitoring of NGS testing for detection of somatic variants and to ensure high quality of sequencing results.
Topics: Genetic Testing; Guidelines as Topic; High-Throughput Nucleotide Sequencing; Humans; Pathology, Molecular; Societies, Medical; United States
PubMed: 28341590
DOI: 10.1016/j.jmoldx.2017.01.011 -
The Journal of Molecular Diagnostics :... Jan 2018Bioinformatics pipelines are an integral component of next-generation sequencing (NGS). Processing raw sequence data to detect genomic alterations has significant impact... (Review)
Review
Standards and Guidelines for Validating Next-Generation Sequencing Bioinformatics Pipelines: A Joint Recommendation of the Association for Molecular Pathology and the College of American Pathologists.
Bioinformatics pipelines are an integral component of next-generation sequencing (NGS). Processing raw sequence data to detect genomic alterations has significant impact on disease management and patient care. Because of the lack of published guidance, there is currently a high degree of variability in how members of the global molecular genetics and pathology community establish and validate bioinformatics pipelines. Improperly developed, validated, and/or monitored pipelines may generate inaccurate results that may have negative consequences for patient care. To address this unmet need, the Association of Molecular Pathology, with organizational representation from the College of American Pathologists and the American Medical Informatics Association, has developed a set of 17 best practice consensus recommendations for the validation of clinical NGS bioinformatics pipelines. Recommendations include practical guidance for laboratories regarding NGS bioinformatics pipeline design, development, and operation, with additional emphasis on the role of a properly trained and qualified molecular professional to achieve optimal NGS testing quality.
Topics: Computational Biology; Guidelines as Topic; High-Throughput Nucleotide Sequencing; Humans; Laboratories; Pathology, Molecular; Reproducibility of Results; United States
PubMed: 29154853
DOI: 10.1016/j.jmoldx.2017.11.003 -
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 -
Head and neck cancer prevention: from primary prevention to impact of clinicians on reducing burden.Annals of Oncology : Official Journal... May 2019Survival from head and neck cancers (HNCs) of the lip, oral cavity, pharynx, and larynx has increased by 10% over the past few decades. Little over half of patients who... (Review)
Review
Survival from head and neck cancers (HNCs) of the lip, oral cavity, pharynx, and larynx has increased by 10% over the past few decades. Little over half of patients who develop HNCs will survive beyond 5 years. Survival is lower for individuals in many countries where traditional risk factors such as tobacco smoking, alcohol drinking, and betel quid chewing are highly prevalent but tertiary health care center access is limited or unavailable. Early diagnosis of HNC is the most important prognostic factor for each tumor site. Molecular-based research on HNC tumors holds promise for early stage detection, screening, vaccination, disease follow-up, and progression. Future investments for HNC control must consider both effectiveness and sustainability for both high- and low-resource countries alike, with priority toward risk factor prevention and earlier diagnosis.
Topics: Head and Neck Neoplasms; Healthy Lifestyle; Humans; Pathology, Molecular; Practice Patterns, Physicians'; Primary Prevention; Treatment Outcome
PubMed: 30840052
DOI: 10.1093/annonc/mdz084 -
Clinical Microbiology Reviews Apr 2011Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these... (Review)
Review
Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs.
Topics: Fungi; Histocytochemistry; Humans; Immunohistochemistry; In Situ Hybridization; Mycoses; Pathology, Molecular; Polymerase Chain Reaction
PubMed: 21482725
DOI: 10.1128/CMR.00053-10 -
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 -
Archives of Pathology & Laboratory... Mar 2018- In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the...
Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
CONTEXT
- In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing.
OBJECTIVE
- To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update.
DESIGN
- The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations.
RESULTS
- Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline.
CONCLUSIONS
- The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes ( ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to "rule in" targetable mutations when tissue is limited or hard to obtain.
Topics: Humans; Antineoplastic Agents; Genetic Testing; Lung Neoplasms; Molecular Targeted Therapy; Pathology, Molecular; Patient Selection; Protein Kinase Inhibitors; United States; Systematic Reviews as Topic
PubMed: 29355391
DOI: 10.5858/arpa.2017-0388-CP -
Cells Dec 2021Lysosomal storage disorders (LSDs) are rare, monogenic diseases characterized by aberrant lysosomes with storage material [...].
Lysosomal storage disorders (LSDs) are rare, monogenic diseases characterized by aberrant lysosomes with storage material [...].
Topics: Animals; Autophagy; Clinical Trials as Topic; Disease Models, Animal; Enzyme Replacement Therapy; Humans; Lysosomal Storage Diseases; Organelles; Pathology, Molecular
PubMed: 35011597
DOI: 10.3390/cells11010036