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==General pathology== [[File:Pathology Lab.png|thumb|A modern pathology lab at the [[Services Institute of Medical Sciences]]]] The modern practice of pathology is divided into a number of subdisciplines within the distinct but deeply interconnected aims of biological research and [[medical practice]]. [[Biomedical research]] into disease incorporates the work of a vast variety of life science specialists, whereas, in most parts of the world, to be [[Medical license|licensed]] to practice pathology as a medical specialty, one has to complete [[medical school]] and secure a license to practice medicine. Structurally, the study of disease is divided into many different fields that study or diagnose markers for disease using methods and technologies particular to specific scales, [[organs]], and tissue types. ===Anatomical pathology=== {{Main|Anatomical pathology}} Anatomical pathology (''Commonwealth'') or anatomic pathology (''United States'') is a medical specialty that is concerned with the diagnosis of disease based on the [[gross examination|gross]], [[Histopathology|microscopic]], chemical, immunologic and [[Molecular pathology|molecular]] examination of organs, tissues, and whole bodies (as in a general examination or an [[autopsy]]). Anatomical pathology is itself divided into subfields, the main divisions being [[surgical pathology]], [[cytopathology]], and [[forensic pathology]]. Anatomical pathology is one of two main divisions of the medical practice of pathology, the other being clinical pathology, the diagnosis of disease through the [[Medical laboratory|laboratory]] analysis of bodily fluids and tissues. Sometimes, pathologists practice both anatomical and clinical pathology, a combination known as general pathology.<ref name="october" /> ====Cytopathology==== {{Main|Cytopathology}} [[File:AML-M6, multinucleated erythroblast.jpg|thumb|right|A [[bone marrow]] [[smear test|smear]] from a case of [[erythroleukemia]]. The large cell in the top center is an abnormal [[erythroblast]]: it is [[multinucleated]], with megaloblastoid [[nucleus (cell)|nuclear]] [[chromatin]]. This is diagnostic of erythroleukemia.]] Cytopathology (sometimes referred to as "cytology") is a branch of pathology that studies and diagnoses diseases on the cellular level. It is usually used to aid in the diagnosis of cancer, but also helps in the diagnosis of certain infectious diseases and other inflammatory conditions as well as thyroid lesions, diseases involving sterile body cavities (peritoneal, pleural, and cerebrospinal), and a wide range of other body sites. Cytopathology is generally used on samples of free cells or tissue fragments (in contrast to histopathology, which studies whole tissues) and cytopathologic tests are sometimes called smear tests because the samples may be smeared across a glass microscope slide for subsequent staining and microscopic examination. However, cytology samples may be prepared in other ways, including [[cytocentrifugation]].<ref>{{Cite book |last=Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson |title=Robbins Basic Pathology |publisher=Philadelphia: Saunders. |year=2007 |isbn=978-1-4160-2973-1 |edition=8th}}</ref> ====Dermatopathology==== {{Main|Dermatopathology}} [[File:Melanoma.jpg|thumb|right|A [[malignant melanoma]] can often be suspected from sight, but confirmation of the diagnosis or outright removal requires a biopsy.]] Dermatopathology is a subspecialty of anatomic pathology that focuses on the skin and the rest of the [[integumentary system]] as an organ. It is unique, in that there are two paths a physician can take to obtain the specialization. All general pathologists and general dermatologists train in the pathology of the skin, so the term [[dermatopathologist]] denotes either of these who has reached a certain level of accreditation and experience; in the US, either a general pathologist or a [[dermatologist]]<ref>{{cite web|url=http://www.abderm.org/subspecialties/derm.html|website = American Board of Dermatology|title=Dermatopathology|url-status=live|archive-url= https://web.archive.org/web/20101207093353/http://www.abderm.org/subspecialties/derm.html|archive-date=2010-12-07}}</ref> can undergo a 1 to 2 year fellowship in the field of dermatopathology. The completion of this fellowship allows one to take a subspecialty board examination, and becomes a board certified dermatopathologist. Dermatologists are able to recognize most skin diseases based on their appearances, anatomic distributions, and behavior. Sometimes, however, those criteria do not lead to a conclusive diagnosis, and a [[skin biopsy]] is taken to be examined under the microscope using usual histological tests. In some cases, additional specialized testing needs to be performed on biopsies, including [[immunofluorescence]], [[immunohistochemistry]], [[electron microscopy]], [[flow cytometry]], and molecular-pathologic analysis.<ref>{{cite web|url=http://www.dermnetnz.org/doctors/dermatopathology/stains.html |title= Special stains and tests – DermNet New Zealand|url-status=live|archive-url=https://web.archive.org/web/20110520143832/http://dermnetnz.org/doctors/dermatopathology/stains.html |archive-date=2011-05-20|date=2008}}</ref> One of the greatest challenges of dermatopathology is its scope. More than 1500 different disorders of the skin exist, including cutaneous eruptions ("[[rashes]]") and [[neoplasms]]. Therefore, dermatopathologists must maintain a broad base of knowledge in clinical dermatology, and be familiar with several other specialty areas in Medicine.<ref>{{Cite web |title=Dermatopathology |url=http://booksfriend.blogspot.com/2010/10/dermatopathology-third-edition-by.html}}</ref> ====Forensic pathology==== {{Main|Forensic pathology}} [[File:Human dissection of the abdominal and toraxic organs.jpg|thumb|Pathologist performing a human dissection of the abdominal and thoracic organs in an autopsy room]] Forensic pathology focuses on determining the cause of death by [[post-mortem examination]] of a corpse or partial remains. An autopsy is typically performed by a coroner or medical examiner, often during criminal investigations; in this role, [[coroner]]s and medical examiners are also frequently asked to confirm the identity of a corpse. The requirements for becoming a licensed practitioner of forensic pathology varies from country to country (and even within a given nation<ref>{{cite journal |author=Lett D |title=National standards for forensic pathology training slow to develop |journal=CMAJ |volume=177 |issue=3 |pages=240–1 |date=July 2007 |pmid=17664437 |pmc=1930175 |doi=10.1503/cmaj.070881 }}</ref>) but typically a minimal requirement is a [[medical doctorate]] with a specialty in general or anatomical pathology with subsequent study in forensic medicine. The methods forensic scientists use to determine death include examination of tissue specimens to identify the presence or absence of natural disease and other microscopic findings, interpretations of [[toxicology]] on body tissues and fluids to determine the chemical cause of overdoses, poisonings or other cases involving toxic agents, and examinations of [[physical trauma]]. Forensic pathology is a major component in the trans-disciplinary field of [[forensic science]].{{cn|date=August 2022}} ====Histopathology==== {{Main|Histopathology}} [[File:Cardiac amyloidosis very high mag movat.jpg|thumb|right|An instance of diagnosis via [[histopathology]], this high-magnification [[micrograph]] of a [[histological section|section]] of cardiac tissue reveals advanced [[cardiac amyloidosis]]. This sample was attained through an [[autopsy]].]] Histopathology refers to the microscopic examination of various forms of [[human tissue]]. Specifically, in clinical medicine, histopathology refers to the examination of a biopsy or surgical specimen by a pathologist, after the specimen has been processed and histological sections have been placed onto glass slides.<ref name="Carson">{{cite book |title=Histotechnology: A Self-Instructional Text |last1=Carson |first1=Freida L |last2=Hladik|first2=Christa |edition=3rd |date=2009 |publisher=[[American Society for Clinical Pathology]] Press |location=Hong Kong |isbn=978-0-89189-581-7 |page=2 }}</ref> This contrasts with the methods of cytopathology, which uses free cells or tissue fragments. Histopathological examination of tissues starts with [[surgery]], [[biopsy]], or autopsy. The tissue is removed from the body of an organism and then placed in a fixative that stabilizes the tissues to prevent decay. The most common fixative is [[formalin]], although [[frozen section]] fixing is also common.<ref>{{cite journal |author= Wilson LB|title= A method for the rapid preparation of fresh tissues for the microscope|journal=J Am Med Assoc|volume=45 |issue= 23|pages=1737|date= 1905|doi=10.1001/jama.1905.52510230037003c|url= https://zenodo.org/record/1423356}}</ref> To see the tissue under a microscope, the sections are stained with one or more pigments. The aim of staining is to reveal cellular components; counterstains are used to provide contrast. Histochemistry refers to the science of using chemical reactions between laboratory chemicals and components within tissue. The histological slides are then interpreted diagnostically and the resulting pathology report describes the histological findings and the opinion of the pathologist. In the case of cancer, this represents the tissue diagnosis required for most treatment protocols. ====Neuropathology==== {{Main|Neuropathology}} [[File:AVM grossly.jpg|thumb|This [[Coronal plane|coronal]] [[Microtome|cross-section]] of a brain reveals a significant [[arteriovenous malformation]] that occupies much of the [[parietal lobe]].]] Neuropathology is the study of disease of nervous system tissue, usually in the form of either surgical biopsies or sometimes whole brains in the case of autopsy. Neuropathology is a subspecialty of anatomic pathology, [[neurology]], and [[neurosurgery]]. In many English-speaking countries, neuropathology is considered a subfield of anatomical pathology. A physician who specializes in neuropathology, usually by completing a fellowship after a residency in anatomical or general pathology, is called a neuropathologist. In day-to-day clinical practice, a neuropathologist generates diagnoses for patients. If a disease of the nervous system is suspected, and the diagnosis cannot be made by less invasive methods, a biopsy of nervous tissue is taken from the brain or spinal cord to aid in diagnosis. Biopsy is usually requested after a mass is detected by [[medical imaging]]. With autopsies, the principal work of the neuropathologist is to help in the post-mortem diagnosis of various conditions that affect the central nervous system. Biopsies can also consist of the skin. Epidermal nerve fiber density testing (ENFD) is a more recently developed neuropathology test in which a [[Skin biopsy#Punch biopsy|punch skin biopsy]] is taken to identify small fiber [[neuropathies]] by analyzing the nerve fibers of the skin. This test is becoming available in select labs as well as many universities; it replaces the traditional nerve biopsy test as less [[invasive surgery|invasive]].{{cn|date=August 2022}} ====Pulmonary pathology==== {{Main|Pulmonary pathology}} [[File:Gross pathology of miliary tuberculosis of the lung.jpg|thumb|151x151px|Gross pathology of miliary tuberculosis of the lung]] Pulmonary pathology is a subspecialty of anatomic (and especially surgical) pathology that deals with diagnosis and characterization of [[neoplasia|neoplastic]] and non-neoplastic diseases of the [[lung]]s and [[thorax|thoracic]] [[pleura]]. Diagnostic specimens are often obtained via [[bronchoscope|bronchoscopic]] transbronchial biopsy, [[Computed tomography|CT]]-guided percutaneous biopsy, or [[thoracic surgery|video-assisted thoracic surgery]]. These tests can be necessary to diagnose between infection, [[inflammation]], or [[fibrosis|fibrotic]] conditions.{{cn|date=August 2022}} ====Renal pathology==== {{Main|Renal pathology}} [[File:Polycystic kidneys, gross pathology CDC PHIL.png|thumb|right|This tissue cross-section demonstrates the gross pathology of [[polycystic kidneys]].]] Renal pathology is a subspecialty of anatomic pathology that deals with the diagnosis and characterization of disease of the [[kidney]]s. In a medical setting, renal pathologists work closely with [[nephrology|nephrologists]] and [[organ transplant|transplant surgeons]], who typically obtain diagnostic specimens via percutaneous renal biopsy. The renal pathologist must synthesize findings from traditional microscope histology, [[electron microscopy]], and [[immunofluorescence]] to obtain a definitive diagnosis. Medical renal diseases may affect the [[Glomerulus (kidney)|glomerulus]], the [[tubules]] and [[interstitium]], the vessels, or a combination of these compartments. ====Surgical pathology==== {{Main|Surgical pathology}} [[File:Brain biopsy under stereotaxy.jpg|thumb|230px|[[Brain biopsy]] under [[stereotaxy]]. A small part of the tumor is taken via a needle with a vacuum system.]] Surgical pathology is one of the primary areas of practice for most anatomical pathologists. Surgical pathology involves the [[Gross pathology|gross]] and microscopic examination of surgical specimens, as well as biopsies submitted by surgeons and non-surgeons such as [[internal medicine|general internists]], [[Medical specialties|medical subspecialists]], [[dermatologists]], and [[radiology|interventional radiologists]]. Often an [[Surgery#Types of surgery|excised]] [[tissue sample]] is the best and most definitive evidence of disease (or lack thereof) in cases where tissue is surgically removed from a patient. These determinations are usually accomplished by a combination of gross (i.e., macroscopic) and histologic (i.e., microscopic) examination of the tissue, and may involve evaluations of molecular properties of the tissue by immunohistochemistry or other laboratory tests.{{cn|date=August 2022}} There are two major types of specimens submitted for surgical pathology analysis: biopsies and surgical resections. A biopsy is a small piece of tissue removed primarily for surgical pathology analysis, most often in order to render a definitive diagnosis. Types of biopsies include core biopsies, which are obtained through the use of large-bore needles, sometimes under the guidance of radiological techniques such as [[ultrasound]], [[CT scan]], or [[magnetic resonance imaging]]. Incisional biopsies are obtained through diagnostic surgical procedures that remove part of a suspicious [[lesion]], whereas excisional biopsies remove the entire lesion, and are similar to therapeutic surgical resections. Excisional biopsies of [[skin lesions]] and [[gastrointestinal]] [[polyps]] are very common. The pathologist's interpretation of a biopsy is critical to establishing the diagnosis of a benign or malignant tumor, and can differentiate between different types and grades of cancer, as well as determining the activity of specific molecular pathways in the tumor. Surgical resection specimens are obtained by the therapeutic surgical removal of an entire diseased area or organ (and occasionally multiple organs). These procedures are often intended as definitive surgical treatment of a disease in which the diagnosis is already known or strongly suspected, but pathological analysis of these specimens remains important in confirming the previous diagnosis.{{cn|date=August 2022}} ===Clinical pathology=== {{Main|Clinical pathology}} Clinical pathology is a medical specialty that is concerned with the diagnosis of disease based on the [[Medical laboratory|laboratory]] analysis of bodily fluids such as blood and [[urine]], as well as tissues, using the tools of [[clinical chemistry|chemistry]], [[clinical microbiology]], [[hematology]] and molecular pathology. Clinical pathologists work in close collaboration with [[medical technologist]]s, hospital administrations, and referring physicians. Clinical pathologists learn to administer a number of visual and microscopic tests and an especially large variety of tests of the [[biophysical]] properties of tissue samples involving [[automated analyser]]s and [[Microbiological culture|culture]]s. Sometimes the general term "laboratory medicine specialist" is used to refer to those working in clinical pathology, including medical doctors, Ph.D.s and doctors of pharmacology.<ref>{{cite news |last1=Zérah |first1=Simone |last2=McMurray |first2=Janet |last3=Horváth |first3=Andrea Rita |title=Our profession now has a European name: Specialist in Laboratory Medicine |url=https://www.eflm.eu/files/efcc/files/EFLM%20Newsletter%202011-05.pdf |archive-url=https://web.archive.org/web/20200323171203/https://www.eflm.eu/files/efcc/files/EFLM%2520Newsletter%25202011-05.pdf |archive-date=2020-03-23 |url-status=live |access-date=23 March 2020 |work=EFCC Newsletter |publisher=European Federation of Clinical Chemistry and Laboratory Medicine |date=May 2011 |location=Paris |page=5}}</ref> [[Immunopathology]], the study of an organism's immune response to infection, is sometimes considered to fall within the domain of clinical pathology.<ref name="bulletin">{{cite web| publisher=Ministère de l'Éducation nationale, de l'Enseignement supérieur et de la Recherche |language=fr|url=http://www.education.gouv.fr/bo/2003/32/MENS0301444A.htm|title=Bulletin officiel du n°32 du 4 septembre 2003 – MENS0301444A|url-status=live|archive-url=https://web.archive.org/web/20080302102242/http://www.education.gouv.fr/bo/2003/32/MENS0301444A.htm|archive-date=2008-03-02|date=4 September 2003}}</ref> ====Hematopathology==== {{Main|Hematopathology}} [[File:Konelab60i.png|thumb|225px|right|[[Clinical chemistry]]: an [[automated analyzer|automated blood chemistry analyzer]]]] Hematopathology is the study of diseases of blood cells (including constituents such as [[white blood cells]], [[red blood cells]], and [[platelets]]) and the tissues, and organs comprising the hematopoietic system. The term hematopoietic system refers to tissues and organs that produce and/or primarily host hematopoietic cells and includes [[bone marrow]], the [[lymph nodes]], [[thymus]], [[spleen]], and other lymphoid tissues. In the United States, hematopathology is a board certified subspecialty (licensed under the American Board of Pathology) practiced by those physicians who have completed a general pathology residency (anatomic, clinical, or combined) and an additional year of fellowship training in hematology. The hematopathologist reviews biopsies of lymph nodes, bone marrows and other tissues involved by an [[Infiltration (medical)|infiltrate]] of cells of the hematopoietic system. In addition, the hematopathologist may be in charge of flow cytometric and/or molecular hematopathology studies.{{cn|date=August 2022}} ===Molecular pathology=== {{Main|Molecular pathology}} Molecular pathology is focused upon the study and diagnosis of disease through the examination of molecules within organs, tissues or [[bodily fluids]].<ref>{{Cite journal|title=The molecular pathology of cancer|author=Harris TJ| author2=McCormick F. |date=2010|journal=Nat Rev Clin Oncol|volume=7|issue=5|pages=251–265|pmid=20351699|pmc=2222796|doi=10.1038/nrclinonc.2010.41}}</ref> Molecular pathology is multidisciplinary by nature and shares some aspects of practice with both anatomic pathology and clinical pathology, [[molecular biology]], [[biochemistry]], [[proteomics]] and [[genetics]]. It is often applied in a context that is as much scientific as directly medical and encompasses the development of molecular and genetic approaches to the diagnosis and classification of human diseases, the design and validation of predictive biomarkers for treatment response and disease progression, and the susceptibility of individuals of different genetic constitution to particular disorders. The crossover between molecular pathology and [[epidemiology]] is represented by a related field "[[molecular pathological epidemiology]]".<ref>{{cite journal |vauthors=Ogino S, Chan AT, Fuchs CS, Giovannucci E | year = 2011 | title = Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field | journal = Gut | volume = 60 | issue = 3| pages = 397–411 | doi=10.1136/gut.2010.217182| pmid = 21036793 | pmc = 3040598}}</ref> Molecular pathology is commonly used in diagnosis of cancer and infectious diseases. Molecular Pathology is primarily used to detect cancers such as melanoma, brainstem glioma, brain tumors as well as many other types of cancer and infectious diseases.<ref>{{cite journal |last1=Zhang |first1=Liwei |last2=Pan |first2=Chang-cun |last3=Li |first3=Deling |title=The historical change of brainstem glioma diagnosis and treatment: from imaging to molecular pathology and then molecular imaging |journal=Chinese Neurosurgical Journal |date=December 2015 |volume=1 |issue=1 |pages=4 |doi=10.1186/s41016-015-0006-3|s2cid=29219804 |doi-access=free }}</ref> Techniques are numerous but include [[quantitative polymerase chain reaction]] (qPCR), [[multiplex polymerase chain reaction|multiplex PCR]], [[DNA microarray]], [[in situ hybridization]], [[DNA sequencing]], antibody-based [[immunofluorescence]] tissue assays, molecular profiling of pathogens, and analysis of bacterial genes for [[antimicrobial resistance]].<ref name=Cai2014>{{cite journal|last=Cai|first=H|author2=Caswell JL|author3=Prescott JF|title=Nonculture Molecular Techniques for Diagnosis of Bacterial Disease in Animals: A Diagnostic Laboratory Perspective|journal=Veterinary Pathology|date=March 2014|volume=51|issue=2|pages=341–350|doi=10.1177/0300985813511132|pmid=24569613|doi-access=|s2cid=206510903}}</ref> Techniques used are based on analyzing samples of DNA and RNA. Pathology is widely used for gene therapy and disease diagnosis.<ref>{{cite journal |last1=Netto |first1=George J |last2=Saad |first2=Rana D |last3=Dysert |first3=Peter A |title=Diagnostic molecular pathology: current techniques and clinical applications, part I. |journal=Proc (Bayl Univ Med Cent) |date=October 2003 |volume=16 |issue=4 |pages=379–83 |doi=10.1080/08998280.2003.11927931 |pmid=16278751 |pmc=1214554}}</ref> ===Oral and maxillofacial pathology=== {{main|Oral and maxillofacial pathology}} [[File:Geographic tongue (cropped).jpg|thumb|220px|right|Many conditions, such as this case of [[geographic tongue]], can be diagnosed partly on gross examination, but may be confirmed with tissue pathology.]] Oral and Maxillofacial Pathology is one of nine dental specialties recognized by the [[American Dental Association]], and is sometimes considered a specialty of both dentistry and pathology.<ref name="Neville 2001">{{cite book|author=Neville BW|author2=Damm DD|author3=Allen CA|author4=Bouquot JE|name-list-style=amp|title=Oral & maxillofacial pathology|date=2002|publisher=W.B. Saunders|location=Philadelphia?page=ix (preface)|isbn=978-0721690032|edition=2nd}}</ref> Oral Pathologists must complete three years of post doctoral training in an accredited program and subsequently obtain diplomate status from the American Board of Oral and Maxillofacial Pathology. The specialty focuses on the diagnosis, clinical management and investigation of diseases that affect the oral cavity and surrounding maxillofacial structures including but not limited to [[Human tooth development|odontogenic]], infectious, [[epithelial]], [[salivary gland]], [[bone]] and [[soft tissue]] pathologies. It also significantly intersects with the field of [[dental pathology]]. Although concerned with a broad variety of diseases of the oral cavity, they have roles distinct from [[otorhinolaryngology|otorhinolaryngologists]] ("ear, nose, and throat" specialists), and [[Speech pathology|speech pathologists]], the latter of which helps diagnose many neurological or [[neuromuscular]] conditions relevant to [[Phonology|speech phonology]] or [[swallowing]]. Owing to the availability of the [[oral cavity]] to non-invasive examination, many conditions in the study of oral disease can be diagnosed, or at least suspected, from gross examination, but biopsies, cell smears, and other tissue analysis remain important diagnostic tools in oral pathology.{{cn|date=August 2022}}
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