Pathology

A renal cell carcinoma (chromophobe type) viewed on a hematoxylin & eosin stained slide

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List of terms related to Pathology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [9]

Pathology is the study and diagnosis of disease through examination of organs, tissues, cells and bodily fluids. The term encompasses both the medical specialty which uses tissues and body fluids to obtain clinically useful information, as well as the related scientific study of disease processes.

History

The histories of both experimental and medical pathology can be traced to the earliest application of the scientific method to the field of medicine, a development which occurred in Western Europe during the Italian Renaissance. Most early pathologists were also practicing physicians or surgeons. Like other medical fields, pathology has become more specialized with time, and most pathologists today do not practice in other areas of medicine.

Origins of pathology

The concept of studying disease through the methodical dissection and examination of diseased bodies, organs, and tissues may seem obvious today, but there are few if any recorded examples of true autopsies performed prior to the Renaissance. The first physician known to have repeatedly used anatomic dissection to determine cause of death was an Italian, Antonio Benivieni (1443-1502). Perhaps the most famous early gross pathologist was Giovanni Morgagni (1682-1771). His magnum opus, De Sedibus et Causis Morborum per Anatomem Indagatis, published in 1761, describes the findings of over 600 partial and complete autopsies, organised anatomically and methodically correlated with the symptoms exhibited by the patients prior to their demise. Although the study of normal anatomy was already well advanced at this date, De Sedibus was one of the first treatises specifically devoted to the corrolation of diseased anatomy with clinical illness. By the late 1800s, an exhaustive body of literature had been produced on the gross anatomical findings characteristic of known diseases. The extent of gross pathology research in this period can be epitomized by the work of the Viennese pathologist (originally from Hradec Kralove in the Czech Rep.) Carl Rokitansky (1804-1878), who is said to have performed 20,000 autopsies, and supervised an additional 60,000, in his lifetime .

Origins of microscopic pathology

Rudolf Virchow (1821-1902) is generally recognized to be the father of microscopic pathology. While the compound microscope had been invented approximately 150 years prior, Virchow was one of the first prominent physicians to emphasize the study of manifestations of disease which were visible only at the cellular level. A student of Virchow's, Julius Cohnheim (1839-1884) combined histology techniques with experimental manipulations to study inflammation, making him one of the earliest experimental pathologists. Cohnheim also pioneered the use of the frozen section; a version of this technique is widely employed by modern pathologists to render diagnoses and provide other clinical information intraoperatively.

Modern experimental pathology

As new research techniques, such as electron microscopy, immunohistochemistry, and molecular biology have expanded the means by which biomedical scientists can study disease, the definition and boundaries of investigative pathology have become less distinct. In the broadest sense, nearly all research which links manifestations of disease to identifiable processes in cells, tissues, or organs can be considered experimental pathology.

Pathology as a science

Pathology is a broad and complex scientific field which seeks to understand the mechanisms of injury to cells and tissues, as well as the body's means of responding to and repairing injury. Disease processes may be incited or exacerbated by a variety of external and internal influences, including trauma, infection, poisoning, loss of blood flow, autoimmunity, inherited or acquired genetic damage, or errors of development. One common theme in pathology is the way in which the body's responses to injury, while evolved to protect health, can also contribute in some ways to disease processes. Elucidation of general principles underlying pathologic processes, such as cellular adaptation to injury, cell death, inflammation, tissue repair, and neoplasia, creates a conceptual framework with which to analyze and understand specific human diseases.

Adaptation to injury

Cells and tissues may respond to injury and stress by specific mechanisms, which may vary according to the cell types and nature of the injury. In the short term, cells may activate specific genetic programs to protect their vital proteins and organelles from heat shock or hypoxia, and may activate DNA repair pathways to repair damage to chromosomes from radiation or chemicals. Hyperplasia is a long-term adaptive response of cell division and multiplication, which can increase the ability of a tissue to compensate for an injury. For example, repeated irritation to the skin can cause a protective thickening due to hyperplasia of the epidermis. Hypertrophy is an increase in the size of cells in a tissue in response to stress, an example being hypertrophy of muscle cells in the heart in response to increased resistance to blood flow as a result of narrowing of the heart's outflow valve. Metaplasia occurs when repeated damage to the cellular lining of an organ triggers its replacement by a different cell type.

Cell death

Necrosis is the irreversible destruction of cells as a result of severe injury in a setting where the cell is unable to activate the needed metabolic pathways for survival or orderly degeneration. This is often due to external pathologic factors, such as toxins or loss of oxygen supply. Milder stresses may lead to a process called reversible cell injury, which mimics the cell swelling and vacuolization seen early in the necrotic process, but in which the cell is able to adapt and survive. In necrosis, the components of degenerating cells leak out, potentially contributing to inflammation and further damage. Apoptosis, in contrast, is a regulated, orderly degeneration of the cell which occurs in the settings of both injury and normal physiological processes.

Inflammation

A transmission electron microscope image of an immune cell crossing from the bone marrow into the circulation

Inflammation is a particularly important and complex reaction to tissue injury, and is particularly important in fighting infection. Acute inflammation is generally a non-specific response triggered by the injured tissue cells themselves, as well as specialized cells of the innate immune system and previously developed adaptive immune mechanisms. A localized acute inflammatory response triggers vascular changes in the injured area, recruits pathogen-fighting neutrophils, and begins the process of developing a new adaptive immune response. Chronic inflammation occurs when the acute response fails to entirely clear the inciting factor. While chronic inflammation can lay a positive role in containing a continuing infectious hazard, it can also lead to progressive tissue damage, as well as predisposing (in some cases) to the development of cancer.

Tissue repair

Tissue repair, as seen in wound healing, is triggered by inflammation. The process may proceed even before the resolution of a precipitating insult, through the formation of granulation tissue. Healing involves the proliferation of connective tissue cells and blood vessel-forming cells as a result of hormonal growth signals. While healing is a critical adaptive response, an aberrent healing response can lead to progressive fibrosis, contractures, or other changes which can compromise function.

Neoplasia

Neoplasia, or "new growth," is a proliferation of cells which is independent of any physiological process. The most familiar examples of neoplasia are benign tumors and cancers. Neoplasia results from genetic changes which cause cells to activate genetic programs inappropriately. Dysplasia is an early sign of a neoplastic process in a tissue, and is marked by persistence of immature, poorly differentiated cell forms. Interestingly, there are many similarities in the gene pathways activated in cancer cells, and those activated in cells involved in wound healing and inflammation.

Pathology as a medical specialty

Physicians who practice pathology diagnose and characterize disease in living patients by examining biopsies and other specimens. For example, the vast majority of cancer diagnoses are made or confirmed by a pathologist. Pathologists may also conduct autopsies to investigate causes of death. The medical practice of pathology grew out the tradition of investigative pathology, and many of the academic leaders in pathology today are accomplished in both basic science research and diagnostic practice. However, as with other specialties in medicine, most modern physician-pathologists are employed in full-time practice, and do not perform original research.

Pathology is a unique medical specialty in that pathologists typically do not see patients directly, but rather serve as consultants to other physicians (often referred to as "clinicians" within the pathology community). However, in the United States and in many other countries, pathologists receive the same doctorate training, and undergo the same medical licensure process as other physicians. Pathology is a diverse field, and the organization of subspecialties within pathology vary between nations.

Anatomical Pathology

This mastectomy specimen contains an infiltrating ductal carcinoma of the breast. A pathologist will use immunohistochemistry and fluorescent in-situ hybridization to detect markers which determine the optimal chemotherapy regimen for this patient.

Main article: Anatomical pathology

Anatomical pathologists diagnose disease and gain other clinically significant information through the examination of tissues and cells. This generally involves gross and microscopic visual examination of tissues, with special stains and immunohistochemistry employed to visualize specific proteins and other substances in and around cells. More recently, anatomical pathologists have begun to employ molecular biology techniques to gain additional clinical information from these same specimens. Anatomic pathologists serve as the definitive diagnosticians for most cancers, as well as numerous other diseases.

• Surgical pathology is the most significant and time-consuming area of practice for most anatomical pathologists. Surgical pathology involves the gross and microscopic examination of surgical specimens, as well as biopsies submitted by non-surgeons such as general internists, medical subspecialists, dermatologists, and interventional radiologists.
• Cytopathology is concerned with the microscopic examination of whole, individual cells obtained from smears or fine needle aspirates.
• Molecular pathology refers to the use of nucleic acid-based techniques, such as in-situ hybridization, reverse-transcriptase polymerase chain reaction, and nucleic acid microarrays for specialised diagnostic studies of disease in tissues and cells.
• Autopsies are used to provide definitive evidence of the disease processes contributing to a person's death.
• Forensic pathology receive specialized training in determining the cause of death and other legally relevant information from the bodies of persons who died in a non-medical or potentially criminal circumstances.

Clinical pathology

Main article: Clinical pathology

Pathogenic organisms are grown from patient specimens in clinical microbiology labs, allowing selection of the correct antibiotics

Clinical pathology, also known as laboratory medicine, is the medical specialty concerned with diagnosing diseases based on the analysis of body fluids, such as plasma, urine, stool, respiratory or mucosal secretions, inflammatory exudates, and pleural, pericardial, peritoneal, synovial, or cerebrospinal fluid. The practice of clinical pathology is centered around the clinical laboratory. In modern clinical laboratories, many routine studies are largely automated. The clinical pathologist is responsible for overseeing the work of laboratory technicians, performing quality assurance to assure the validity of test results, performing interpretations of more complex studies, and serving as a consultant to clinicians so that the most appropriate studies can be performed for the diagnosis or assessment of an individual patient's condition. In some areas, non-pathologists, such as other physicians or Ph.D.'s may run clinical labs and perform functions within those specific labs which are similar to the role of a board-certified clinical pathologist.

Sub-specialties within clinical pathology include the following:

• Clinical chemistry (A board-certifiable subspecialty, chemical pathology, in the U.S.)
• Hematology and Flow cytometry (Part of a board-certifiable subspecialty, hematology, in the U.S.)
• Blood banking/Transfusion medicine (A board-certifiable subspecialty in the U.S.)
• Medical microbiology (A board-certifiable subspecialty in the U.S.)
• Medical cytogenetics
• Immunology
• Molecular genetic pathology (A board-certifiable subspecialty in the U.S.)

Dental pathology

In the United States, subspecialty-trained doctors of dental surgery (D.D.S), rather than medical doctors, can be certified by a professional board to practice dental pathology.

Training of medical pathologists

Pathology in the United States

In the United States, pathologists are medical doctors (M.D.) or doctors of osteopathic medicine (D.O.), that have completed a four-year undergraduate program, four years of medical school training, and three to four years of postgraduate training in the form of a pathology residency. Training may be within two primary specialties, as recognized by the American Board of Pathology: Anatomic Pathology, and Clinical Pathology, each of which requires separate board certification. Many pathologists seek a broad-based training and become certified in both fields. These skills are complementary in many hospital-based private practice settings, since the day-to-day work of many clinical laboratories only requires the intermittent attention of a physician. Thus, pathologists are able to spend much of their time evaluating anatomic pathology cases, while remaining available to cover any special issues which might arise in the clinical laboratories. Pathologists may pursue specialised fellowship training within one or more sub-specialties of either anatomic or clinical pathology. Some of these sub-specialities permit additional board certification, while others do not.

Pathology in the United Kingdom

In the UK pathologists are medical doctors registered with the UK General Medical Council. They will have completed an undergraduate medical education which in most countries lasts 4-6 years. The training to become a pathologist is under the oversight of the Royal College of Pathologists. Typically a one year training attachment is followed by an aptitude test. This is followed by further specialist training in surgical pathology, cytopathology, and post mortem pathology. There are two examinations run by the Royal College of Pathologists termed Part 1 and Part 2. The Part 2 examination is designed to test competence to work as an independent practitioner in pathology and is typically taken after 5 years specialist training. All post-graduate medical training and education in the UK is overseen by the Postgraduate Medical Education and Training Board. It is possible to take a specialist part 2 examination in paediatric pathology or neuropathology. It is possible to take a special diploma in dermatopathology or cytopathology, recognising additional specialist training and expertise.

Non-human pathology

Veterinary pathologists are veterinary practitioners who specialise in the diagnosis and characterization of veterinary diseases through the examination of animal tissue and body fluids. Veterinary pathologists are veterinarians with advanced training (board certification or Ph.D.) in either diagnostic pathology or research into the biological processes underlying disease (pathobiology). Diagnostic veterinary pathologists are further subcategorized as either anatomical pathologists or clinical pathologists. Clinical pathologists examine specimens such as blood, excretions or biopsy material to diagnose disease in living animals. Anatomical pathologists utilize post mortem examinations of dead animals to arrive at a diagnosis. Post mortem examinations entail a necropsy (an animal autopsy), histopathologic (microscopic) study of tissue specimens collected at the necropsy and sometimes specialized studies (radiographic, toxicologic, etc.)

Plant pathologists are specialized scientists who investigate the causes of diseases in plants.

See also

• Important publications in pathology

External links

• American Society for Investigative Pathology
• American Society of Cytopathology
• British Neuropathological Society
• Case Records of the Massachusetts General Hospital - Clinicopathological Conference
• College of American Pathologists
• Immunohistochemistry protocols and troubleshooting
• Pathological Society of Great Britain and Ireland
• Royal College of Pathologists (UK)
• Sullivan Nicolaides Pathology - Leading Australian Pathology Laboratory.
• United States and Canadian Academy of Pathology
• WebPath: The Internet Pathology Laboratory for Medical Education
• What is a Pathologist? - a perspective from UK pathologist Fraser Charlton.
• Royal College of Pathologists (UK)
• HistoPathology Atlas

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