Cytopathology
Encyclopedia
Cytopathology is a branch of pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....

 that studies and diagnoses diseases on the cellular level. The discipline was founded by Rudolf Virchow
Rudolf Virchow
Rudolph Carl Virchow was a German doctor, anthropologist, pathologist, prehistorian, biologist and politician, known for his advancement of public health...

 in 1858. A common application of cytopathology is the Pap smear
Pap smear
The Papanicolaou test is a screening test used in to detect pre-cancerous and cancerous processes in the endocervical canal of the female reproductive system. Changes can be treated, thus preventing cervical cancer...

, used as a screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....

 tool, to detect precancerous
Cervical intraepithelial neoplasia
Cervical intraepithelial neoplasia , also known as cervical dysplasia and cervical interstitial neoplasia, is the potentially premalignant transformation and abnormal growth of squamous cells on the surface of the cervix. CIN is not cancer, and is usually curable...

 cervical lesions and prevent cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...

. Cytopathology is also commonly used to investigate thyroid lesions, diseases involving sterile body cavities (peritoneal, pleural, and cerebrospinal), and a wide range of other body sites. 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. Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to histopathology
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...

, which studies whole tissues.

Cytopathologic tests are sometimes called smear tests because the samples may be smeared across a glass microscope slide
Microscope slide
A microscope slide is a thin flat piece of glass, typically 75 by 25 mm and about 1 mm thick, used to hold objects for examination under a microscope. Typically the object is placed or secured on the slide, and then both are inserted together in the microscope for viewing...

 for subsequent staining and microscopic examination. However, cytology samples may be prepared in other ways, including cytocentrifugation. Different types of smear tests may also be used for cancer diagnosis. In this sense, it is termed a cytologic smear.

Cytopathology is frequently, less precisely, called cytology
Cytology
Cytology means "the study of cells".Cytology is that branch of life science, which deals with the study of cells in terms of structure, function and chemistry.Based on usage it can refer to:...

, which means "the study of cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

s."

Cell collection

Two methods of collecting cells for cytopathologic analysis are:
  1. Exfoliative Cytology – In this method, cells are collected after they have been either spontaneously shed by the body ("spontaneous exfoliation") or manually scraped/brushed off of a surface in the body ("mechanical exfoliation"). An example of spontaneous exfoliation is when cells of the pleural cavity
    Pleural cavity
    In human anatomy, the pleural cavity is the potential space between the two pleura of the lungs. The pleura is a serous membrane which folds back onto itself to form a two-layered, membrane structure. The thin space between the two pleural layers is known as the pleural cavity; it normally...

     or peritoneal cavity
    Peritoneal cavity
    The peritoneal cavity is a potential space between the parietal peritoneum and visceral peritoneum, that is, the two membranes that separate the organs in the abdominal cavity from the abdominal wall...

     are shed into the pleural or peritoneal fluid. This fluid can be collected via various methods for examination. Examples of mechanical exfoliation include Pap smears, where cells are scraped from the cervix with a cervical spatula, or bronchial brushings, where a bronchoscope is inserted into the trachea
    Vertebrate trachea
    In tetrapod anatomy the trachea, or windpipe, is a tube that connects the pharynx or larynx to the lungs, allowing the passage of air. It is lined with pseudostratified ciliated columnar epithelium cells with goblet cells that produce mucus...

     and used to evaluate a visible lesion by brushing cells from its surface and subjecting them to cytopathologic analysis.
  2. intervention cytology- in interventional cytology the pathologist intervenes into the body for sample collection. Nowadays FNAC has become synonymous to interventional cytology.


1. Fine-Needle Aspiration Cytology or Needle aspiration biopsy
Needle aspiration biopsy
Needle aspiration biopsy , may refer to fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...

 – A needle
Hypodermic needle
A hypodermic needle is a hollow needle commonly used with a syringe to inject substances into the body or extract fluids from it...

 attached to a syringe
Syringe
A syringe is a simple pump consisting of a plunger that fits tightly in a tube. The plunger can be pulled and pushed along inside a cylindrical tube , allowing the syringe to take in and expel a liquid or gas through an orifice at the open end of the tube...

 is used to collect cells from lesions or masses in various body organs by microcoring, often with the application of negative pressure (suction) to increase yield. FNAC can be performed under palpation guidance (i.e., the clinician can feel the lesion) on a mass in superficial regions like the neck, thyroid or breast; FNAC may also be assisted by ultrasound
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...

 or CAT scan for sampling of deep-seated lesions within the body that cannot be localized via palpation. FNAC is widely used in many countries, but success rate is dependent on the skill of the practitioner. If performed by a pathologist alone, or as team with pathologist-cytotechnologist, the success rate of proper diagnosis is superior than when performed by a non-pathologist. This may be due to the pathologist's ability to immediately evaluate specimens under a microscope and immediately repeat the procedure if sampling was inadequate.

Fine needles are 23 to 27 gauge. Because needles as small as 27 gauge can almost always yield diagnostic material, FNAC is often the least injurious way to obtain diagnostic tissue from a lesion. Sometime a syringe holder may be used to facilitate using one hand to perform the biopsy while the other hand is immobilizing the mass. Imaging equipment such as a CT scanner or ultrasound may be used to assist in locating the region to be biopsied.

2. Sediment cytology – Here, the sample is collected from the fixative that was used for processing the biopsy or autopsy specimen. The fixative is mixed properly and taken into a centrifuge tube and is centrifuged. The sediment is used for smearing. These sediments are the cells that are shed by the autopsy and biopsy specimen during processing.

Parameters

The nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

 of the cell is very important in evaluating the cellular sample. In cancerous cells, altered DNA activity can be seen as a physical change in the nuclear qualities. Since more DNA is unfolded and being expressed, the nucleus will be darker and less uniform, larger than in normal cells, and often show a bright-red nucleolus
Nucleolus
The nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...

.

While the cytologist's primary responsibility is to discern whether cancerous or precancerous pathology is present in the cellular sample analysed, other pathologies may be seen such as:
  • microbial infections: parasitic, viral, and/or bacterial
  • reactive changes
  • immune reactions
  • cell aging
  • amyloidosis
    Amyloidosis
    In medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...

  • autoimmune diseases


Various normal functions of cell growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...

, metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

, and division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...

 can fail or work in abnormal ways and lead to diseases.

Cytopathology is best used as one of three tools, the second and third being the physical exam and medical imaging
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...

. Cytology can be used to diagnose a condition and spare a patient from surgery to obtain a larger specimen. An example is thyroid FNA; many benign conditions can be diagnosed with a superficial biopsy and the patient can go back to normal activities right away. If a malignant condition is diagnosed, the patient may be able to start radiation/chemotherapy, or may need to have surgery to remove and/or stage the cancer.

Some tumors may be difficult to biopsy, such as sarcomas. Other rare tumors my be dangerous to biopsy, such as pheochromocytoma
Pheochromocytoma
A pheochromocytoma or phaeochromocytoma is a neuroendocrine tumor of the medulla of the adrenal glands , or extra-adrenal chromaffin tissue that failed to involute after birth and secretes excessive amounts of catecholamines, usually noradrenaline , and adrenaline to a lesser extent...

. In general, a fine-needle aspiration can be done anywhere it is safe to put a needle, including liver, lung, kidney, and superficial masses.

Many clinicians are not trained to perform fine-needle aspiration biopsies properly and, then when they do not obtain diagnostic material, believe that cytology is not useful. Proper technique takes time to master. Cytotechnologists and cytopathologists can assist clinicians by going to procedures and assisting with collection techniques. A "quick read" is a peek under the microscope and can tell the clinician whether enough diagnostic material was obtained. Cytological specimens must also be properly prepared so that the cells are not damaged.

Sometimes more information about the specimen is helpful. Immunohistochemical stains and molecular testing can be performed, especially if the sample is prepared using liquid based cytology. Often "reflex" testing is performed, such as HPV testing on an abnormal pap test or flow cytometry
Flow cytometry
Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical...

 on a lymphoma specimen.

Body regions

Cytopathologic techniques are used in the examination of virtually all body organs
Organ (anatomy)
In biology, an organ is a collection of tissues joined in structural unit to serve a common function. Usually there is a main tissue and sporadic tissues . The main tissue is the one that is unique for the specific organ. For example, main tissue in the heart is the myocardium, while sporadic are...

 and tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

:
  • Gynaecologic cytology
    Gynaecologic cytology
    Gynaecologic cytology, also gynaecologic cytopathology, is a field of pathology is concerned with the investigation of disorders of the female genital tract....

     - concerning the female reproductive tract
  • Urinary tract cytology - concerning the ureter
    Ureter
    In human anatomy, the ureters are muscular tubes that propel urine from the kidneys to the urinary bladder. In the adult, the ureters are usually long and ~3-4 mm in diameter....

    s, urinary bladder
    Urinary bladder
    The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...

     and urethra
    Urethra
    In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...

  • Effusion cytology - concerning fluids collections, especially within the peritoneum
    Peritoneum
    The peritoneum is the serous membrane that forms the lining of the abdominal cavity or the coelom — it covers most of the intra-abdominal organs — in amniotes and some invertebrates...

    , pleura and pericardium
    Pericardium
    The pericardium is a double-walled sac that contains the heart and the roots of the great vessels.-Layers:...

  • Breast cytology - principally concerning the female breast
    Breast
    The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...

  • Thyroid cytology - concerning the thyroid gland
  • Lymph node cytology - concerning lymph node
    Lymph node
    A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

    s
  • Respiratory cytology - concerning the lung
    Lung
    The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

    s and airways
  • Gastrointestinal cytology - concerning the alimentary tract
  • Soft tissue, bone and skin cytology
  • Kidney and adrenal cytology
  • Liver and pancreas cytology
  • Central nervous system cytology
  • Eye cytology
  • Salivary gland cytology

See also

  • American Society of Cytopathology
    American Society of Cytopathology
    The [American Society of Cytopathology ], founded in 1951, is a national professional society of physicians, cytotechnologists and scientists who are dedicated to the cytologic method of diagnostic pathology. They have more than 3500 members including representatives for other countries. The ASC...

  • Cell biology
    Cell biology
    Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...

  • Clinical pathology
    Clinical pathology
    Clinical pathology , Laboratory Medicine , Clinical analysis or Clinical/Medical Biology , is a medical specialty that is concerned with the diagnosis of disease based on the laboratory analysis of bodily fluids, such as...

  • Anatomical pathology
    Anatomical pathology
    Anatomical pathology or Anatomic pathology is a medical specialty that is concerned with the diagnosis of disease based on the gross, microscopic, chemical, immunologic and molecular examination of organs, tissues, and whole bodies...

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