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Molecular Medicine Reports Jan 2022Efferocytosis, the phagocytosis of apoptotic cells performed by both specialized phagocytes (such as macrophages) and non‑specialized phagocytes (such as epithelial... (Review)
Review
Efferocytosis, the phagocytosis of apoptotic cells performed by both specialized phagocytes (such as macrophages) and non‑specialized phagocytes (such as epithelial cells), is involved in tissue repair and homeostasis. Effective efferocytosis prevents secondary necrosis, terminates inflammatory responses, promotes self‑tolerance and activates pro‑resolving pathways to maintain homeostasis. When efferocytosis is impaired, apoptotic cells that could not be cleared in time aggregate, resulting in the necrosis of apoptotic cells and release of pro‑inflammatory factors. In addition, defective efferocytosis inhibits the intracellular cholesterol reverse transportation pathways, which may lead to atherosclerosis, lung damage, non‑alcoholic fatty liver disease and neurodegenerative diseases. The uncleared apoptotic cells can also release autoantigens, which can cause autoimmune diseases. Cancer cells escape from phagocytosis via efferocytosis. Therefore, new treatment strategies for diseases related to defective efferocytosis are proposed. This review illustrated the mechanisms of efferocytosis in multisystem diseases and organismal homeostasis and the pathophysiological consequences of defective efferocytosis. Several drugs and treatments available to enhance efferocytosis are also mentioned in the review, serving as new evidence for clinical application.
Topics: Animals; Apoptosis; Cytophagocytosis; Disease; Epithelial Cells; Extracellular Vesicles; Homeostasis; Humans; Immunity; Inflammation; Macrophages; Necrosis; Pathology; Phagocytes
PubMed: 34779503
DOI: 10.3892/mmr.2021.12529 -
Pathologie (Heidelberg, Germany) Aug 2022Odontogenic tumors (OTs) are rare, with an estimated incidence rate of less than 0.5 cases per 100,000 per year. The causes of OTs remain unclear. Nonetheless, the... (Review)
Review
BACKGROUND
Odontogenic tumors (OTs) are rare, with an estimated incidence rate of less than 0.5 cases per 100,000 per year. The causes of OTs remain unclear. Nonetheless, the majority of OTs seem to arise de novo, without an apparent causative factor. Although the etiopathogenesis of most OTs remains unclear, there have been some recent advances in understanding the genetic basis relating to specific histologies and clinical features. Molecular analyses performed by different techniques, including Sanger sequencing, next-generation sequencing, and allele-specific PCR, have uncovered mutations in genes related to the oncogenic MAPK/ERK signaling pathway. Genetic mutations in these pathway genes have been reported in epithelial and mixed OTs, in addition to odontogenic carcinomas and sarcomas. Notably, B‑RAF proto-oncogene serine/threonine kinase (BRAF) and KRAS proto-oncogene GTPase (KRAS) pathogenic mutations have been reported in a high proportion of ameloblastoma and ameloblastoma-related tumors and adenomatoid odontogenic tumors, respectively.
OBJECTIVE
To discuss how molecular profiling aids in diagnostic classification of odontogenic tumors.
CONCLUSION
Molecular profiling of odontogenic tumors helps to identify patients for neoadjuvant therapies and reduces postoperative morbidity.
Topics: Humans; Ameloblastoma; Odontogenic Tumors; Pathology, Molecular; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 36378285
DOI: 10.1007/s00292-022-01152-7 -
Archives of Pathology & Laboratory... Oct 2022The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or...
Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: Guideline From the College of American Pathologists in Collaboration With the Association for Molecular Pathology and Fight Colorectal Cancer.
CONTEXT.—
The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or high levels of microsatellite instability; however, the FDA provided no guidance on which specific clinical assays should be used to determine mismatch repair status.
OBJECTIVE.—
To develop an evidence-based guideline to identify the optimal clinical laboratory test to identify defects in DNA mismatch repair in patients with solid tumor malignancies who are being considered for immune checkpoint inhibitor therapy.
DESIGN.—
The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Using the National Academy of Medicine-endorsed Grading of Recommendations Assessment, Development and Evaluation approach, the recommendations were derived from available evidence, strength of that evidence, open comment feedback, and expert panel consensus. Mismatch repair immunohistochemistry, microsatellite instability derived from both polymerase chain reaction and next-generation sequencing, and tumor mutation burden derived from large panel next-generation sequencing were within scope.
RESULTS.—
Six recommendations and 3 good practice statements were developed. More evidence and evidence of higher quality were identified for colorectal cancer and other cancers of the gastrointestinal (GI) tract than for cancers arising outside the GI tract.
CONCLUSIONS.—
An optimal assay depends on cancer type. For most cancer types outside of the GI tract and the endometrium, there was insufficient published evidence to recommend a specific clinical assay. Absent published evidence, immunohistochemistry is an acceptable approach readily available in most clinical laboratories.
Topics: Female; Humans; Colorectal Neoplasms; DNA Mismatch Repair; Immune Checkpoint Inhibitors; Microsatellite Instability; Pathologists; Pathology, Molecular; Systematic Reviews as Topic
PubMed: 35920830
DOI: 10.5858/arpa.2021-0632-CP -
Wiener Medizinische Wochenschrift (1946) Sep 2021Dementia is the clinical consequence of various neurological disorders with a multitude of etiologies. Precise knowledge of the underlying pathologies is essential for... (Review)
Review
Dementia is the clinical consequence of various neurological disorders with a multitude of etiologies. Precise knowledge of the underlying pathologies is essential for an accurate treatment of patients and for the development of suitable disease biomarkers. A definite diagnosis of many of the disorders, particularly for neurodegenerative ones, can only be made after a thorough postmortem neuropathological examination. This highlights the importance of performing a brain autopsy and the relevance of a close interaction between clinicians, neuroimaging disciplines and neuropathologists as well as with basic researchers. This article aims to give a brief overview on the neuropathology of dementia focusing on neurodegenerative diseases, to further facilitate interdisciplinary collaboration.
Topics: Autopsy; Brain; Dementia; Humans; Neurodegenerative Diseases; Neuropathology
PubMed: 34129141
DOI: 10.1007/s10354-021-00848-4 -
Clinical Journal of the American... Jan 2022Biomarkers for noninvasive assessment of histopathology and prognosis are needed in patients with kidney disease.
BACKGROUND AND OBJECTIVES
Biomarkers for noninvasive assessment of histopathology and prognosis are needed in patients with kidney disease.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Using a proteomics assay, we measured a multimarker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semiquantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or initiation of KRT) and death.
RESULTS
After multivariable adjustment and correction for multiple testing, 46 different proteins were associated with histopathologic lesions. The top-performing markers positively associated with acute tubular injury and interstitial fibrosis/tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and Ig domain-containing protein 2 (VSIG2), respectively. Thirty proteins were significantly associated with kidney disease progression, and 35 were significantly associated with death. The top-performing markers for kidney disease progression were placental growth factor (hazard ratio per doubling, 5.4; 95% confidence interval, 3.4 to 8.7) and BMP and activin membrane-bound inhibitor (hazard ratio, 3.0; 95% confidence interval, 2.1 to 4.2); the top-performing markers for death were TNF-related apoptosis-inducing ligand receptor-2 (hazard ratio, 2.9; 95% confidence interval, 2.0 to 4.0) and CUB domain-containing protein-1 (hazard ratio, 2.4; 95% confidence interval, 1.8 to 3.3).
CONCLUSION
We identified several plasma protein biomarkers associated with kidney disease histopathology and adverse clinical outcomes in individuals with a diverse set of kidney diseases.
PODCAST
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_12_28_CJN09380721.mp3.
Topics: Adult; Aged; Biomarkers; Biopsy; Female; Humans; Kidney Diseases; Male; Middle Aged
PubMed: 34759008
DOI: 10.2215/CJN.09380721 -
British Journal of Biomedical Science 2023Diagnosis of superficial/cutaneous fungal infections from skin, hair and nail samples is generally achieved using microscopy and culture in a microbiology laboratory,... (Review)
Review
Diagnosis of superficial/cutaneous fungal infections from skin, hair and nail samples is generally achieved using microscopy and culture in a microbiology laboratory, however, any presentation that is unusual or subcutaneous is sampled by taking a biopsy. Using histological techniques a tissue biopsy enables a pathologist to perform a full examination of the skin structure, detect any inflammatory processes or the presence of an infectious agent or foreign body. Histopathological examination can give a presumptive diagnosis while a culture result is pending, and may provide valuable diagnostic information if culture fails. This review demonstrates how histopathology contributes to the diagnosis of fungal infections from the superficial to the life threatening.
Topics: Humans; Dermatomycoses; Biopsy
PubMed: 37351018
DOI: 10.3389/bjbs.2023.11314 -
Archives of Pathology & Laboratory... May 2020To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen receptor (ER) and progesterone receptor (PgR)...
PURPOSE.—
To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer guideline.
METHODS.—
A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature.
RECOMMENDATIONS.—
The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines .
Topics: Female; Humans; American Medical Association; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Estrogens; Immunohistochemistry; Medical Oncology; Pathologists; Pathology, Clinical; Prognosis; Receptors, Progesterone; United States; Systematic Reviews as Topic
PubMed: 31928354
DOI: 10.5858/arpa.2019-0904-SA -
Nature Communications Oct 2023Current diagnosis of glioma types requires combining both histological features and molecular characteristics, which is an expensive and time-consuming procedure....
Current diagnosis of glioma types requires combining both histological features and molecular characteristics, which is an expensive and time-consuming procedure. Determining the tumor types directly from whole-slide images (WSIs) is of great value for glioma diagnosis. This study presents an integrated diagnosis model for automatic classification of diffuse gliomas from annotation-free standard WSIs. Our model is developed on a training cohort (n = 1362) and a validation cohort (n = 340), and tested on an internal testing cohort (n = 289) and two external cohorts (n = 305 and 328, respectively). The model can learn imaging features containing both pathological morphology and underlying biological clues to achieve the integrated diagnosis. Our model achieves high performance with area under receiver operator curve all above 0.90 in classifying major tumor types, in identifying tumor grades within type, and especially in distinguishing tumor genotypes with shared histological features. This integrated diagnosis model has the potential to be used in clinical scenarios for automated and unbiased classification of adult-type diffuse gliomas.
Topics: Adult; Humans; Brain Neoplasms; Deep Learning; Neuropathology; Glioma
PubMed: 37821431
DOI: 10.1038/s41467-023-41195-9 -
Turk Patoloji Dergisi 2023In Turkey, autopsy performers, namely forensic medicine practitioners, are neither pathologists nor have properly received pathology training during residency in...
OBJECTIVE
In Turkey, autopsy performers, namely forensic medicine practitioners, are neither pathologists nor have properly received pathology training during residency in contrast to the Anglo-Saxon model of forensic medicine practices, since the current curriculum of forensic medicine residency lacks adequate training in post-mortem histopathology. Likewise, pathologists lack a specific post-mortem pathology clerkship. In this study, we intended to determine whether forensic physicians in Turkey find themselves competent in post-mortem histopathology or were adequately trained during their residencies.
MATERIAL AND METHOD
Turkish forensic medicine practitioners were administered an online questionnaire whereby self-evaluations of their histopathology knowledge and their views on histopathology training during forensic medicine residency were assessed. The 151 physicians who completed the questionnaire made up the study group.
RESULTS
It was found out that the majority of Turkish forensic medicine practitioners (85.4%) did not find the histopathology training during their residency adequate. Similarly, 85.4% of the participants indicated their incompetence in histopathological examination of post-mortem tissue of any kind, and showed their willingness for further training in pathology. 66.9% strongly agreed that post-mortem histopathology requires training that is distinct from surgical pathology. In case of providing post-mortem histopathology training within the scope of forensic medicine residency, topics such as microscopic morphology of post-mortem changes, histological changes related to injuries, and estimation of wound age are expected to be beneficial to 88.7% 83.4%, and 83.4% of the participants respectively.
CONCLUSION
The current curriculum should be revised in a way that the surgical pathology clerkship meets forensic physicians' needs, so that they can then refer more difficult, non-routine histopathological consultations to pathologists who are also well-trained in postmortem histopathology. Consideration should also be given to establishing a subspecialty training - a master's or doctoral degree programs in forensic pathology.
Topics: Humans; Autopsy; Forensic Medicine; Pathologists; Pathology, Surgical; Turkey
PubMed: 35102540
DOI: 10.5146/tjpath.2022.01569 -
Analytical Chemistry Oct 2019Fourier transform-infrared spectroscopy (FT-IR) represents an attractive molecular diagnostic modality for translation to the clinic, where comprehensive chemical... (Review)
Review
Fourier transform-infrared spectroscopy (FT-IR) represents an attractive molecular diagnostic modality for translation to the clinic, where comprehensive chemical profiling of biological samples may revolutionize a myriad of pathways in clinical settings. Principally, FT-IR provides a rapid, cost-effective platform to obtain a molecular fingerprint of clinical samples based on vibrational transitions of chemical bonds upon interaction with infrared light. To date, considerable research activities have demonstrated competitive to superior performance of FT-IR strategies in comparison to conventional techniques, with particular promise for earlier, accessible disease diagnostics, thereby improving patient outcomes. However, amidst the changing healthcare landscape in times of aging populations and increased prevalence of cancer and chronic disease, routine adoption of FT-IR within clinical laboratories has remained elusive. Hence, this perspective shall outline the significant clinical potential of FT-IR diagnostics and subsequently address current barriers to translation from the perspective of all stakeholders, in the context of biofluid, histopathology, cytology, microbiology, and biomarker discovery frameworks. Thereafter, future perspectives of FT-IR for healthcare will be discussed, with consideration of recent technological advances that may facilitate future clinical translation.
Topics: Bacterial Infections; Biomarkers; Body Fluids; Humans; Pathology, Clinical; Precision Medicine; Spectroscopy, Fourier Transform Infrared; Translational Research, Biomedical
PubMed: 31503460
DOI: 10.1021/acs.analchem.9b02280