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A pair of micrographs of a cytopathology specimen showing a 3-dimensional cluster of cancerous cells (serous carcinoma) Serous carcinoma 2c - cytology.gif
A pair of micrographs of a cytopathology specimen showing a 3-dimensional cluster of cancerous cells (serous carcinoma)

Cytopathology (from Greek κύτος, kytos, "a hollow"; [1] πάθος, pathos, "fate, harm"; and -λογία, -logia ) is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by George Nicolas Papanicolaou in 1928. Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to histopathology, which studies whole tissues.

Ancient Greek Version of the Greek language used from roughly the 9th century BCE to the 6th century CE

The Ancient Greek language includes the forms of Greek used in Ancient Greece and the ancient world from around the 9th century BCE to the 6th century CE. It is often roughly divided into the Archaic period, Classical period, and Hellenistic period. It is antedated in the second millennium BCE by Mycenaean Greek and succeeded by medieval Greek.

-logy is a suffix in the English language, used with words originally adapted from Ancient Greek ending in -λογία (-logia). The earliest English examples were anglicizations of the French -logie, which was in turn inherited from the Latin -logia. The suffix became productive in English from the 18th century, allowing the formation of new terms with no Latin or Greek precedent.

Pathology study and diagnosis of disease

Pathology is the study of the causes and effects of disease or injury. The word pathology also refers to the study of disease in general, incorporating a wide range of bioscience research fields and medical practices. However, when used in the context of modern medical treatment, the term is often used in a more narrow fashion to refer to processes and tests which fall within the contemporary medical field of "general pathology," an area which includes a number of distinct but inter-related medical specialties that diagnose disease, mostly through analysis of tissue, cell, and body fluid samples. Idiomatically, "a pathology" may also refer to the predicted or actual progression of particular diseases, and the affix path is sometimes used to indicate a state of disease in cases of both physical ailment and psychological conditions. A physician practicing pathology is called a pathologist.


Cytopathology is commonly used to investigate diseases involving a wide range of body sites, often to aid in the diagnosis of cancer but also in the diagnosis of some infectious diseases and other inflammatory conditions. For example, a common application of cytopathology is the Pap smear, a screening tool used to detect precancerous cervical lesions that may lead to cervical cancer.

Screening (medicine) testing a group or population for disease

Screening, in medicine, is a strategy used in a population to identify the possible presence of an as-yet-undiagnosed disease in individuals without signs or symptoms. This can include individuals with pre-symptomatic or unrecognized symptomatic disease. As such, screening tests are somewhat unusual in that they are performed on persons apparently in good health.

Cervical intraepithelial neoplasia

Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous transformation of cells of the cervix.

Cervical cancer cancer arising from the cervix, caused by a sexually transmitted virus

Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal vaginal bleeding, pelvic pain, or pain during sexual intercourse. While bleeding after sex may not be serious, it may also indicate the presence of cervical cancer.

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. Different types of smear tests may also be used for cancer diagnosis. In this sense, it is termed a cytologic smear. [2]

Microscope slide

A microscope slide is a thin flat piece of glass, typically 75 by 26 mm and about 1 mm thick, used to hold objects for examination under a microscope. Typically the object is mounted (secured) on the slide, and then both are inserted together in the microscope for viewing. This arrangement allows several slide-mounted objects to be quickly inserted and removed from the microscope, labeled, transported, and stored in appropriate slide cases or folders etc.

Cytopathology is frequently, less precisely, called cytology, which means "the study of cells". [3]

Cell biology scientific discipline that studies cells

Cell biology is a branch of biology that studies the structure and function of the cell, which is the basic unit of life. Cell biology is concerned with the physiological properties, metabolic processes, signaling pathways, life cycle, chemical composition and interactions of the cell with their environment. This is done both on a microscopic and molecular level as it encompasses prokaryotic cells and eukaryotic cells. Knowing the components of cells and how cells work is fundamental to all biological sciences; it is also essential for research in bio-medical fields such as cancer, and other diseases. Research in cell biology is closely related to genetics, biochemistry, molecular biology, immunology and cytochemistry.

Cell (biology) The basic structural and functional unit of all organisms; the smallest unit of life.

The cell is the basic structural, functional, and biological unit of all known living organisms. A cell is the smallest unit of life. Cells are often called the "building blocks of life". The study of cells is called cell biology or cellular biology.

Micrograph of a pilocytic astrocytoma, showing characteristic bipolar cells with long pilocytic (hair-like) processes. Smear preparation. H&E stain Pilocytic astrocytoma - smear - very high mag.jpg
Micrograph of a pilocytic astrocytoma, showing characteristic bipolar cells with long pilocytic (hair-like) processes. Smear preparation. H&E stain

Cell collection

There are two methods of collecting cells for cytopathologic analysis: exfoliative cytology, and intervention cytology.

Exfoliative cytology

A micrograph of an exfoliative cytopathology specimen (Pap test, Pap stain) Low-grade squamous intraepithelial lesion.jpg
A micrograph of an exfoliative cytopathology specimen (Pap test, Pap stain)

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 or peritoneal cavity 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 and used to evaluate a visible lesion by brushing cells from its surface and subjecting them to cytopathologic analysis. After sampling, two main techniques can be used; Conventional cytology and Liquid-based cytology. With the latter, we place the sample in a liquid that is then processed and allows for further investigation to be made.

Pleural cavity thin fluid-filled space between the two pulmonary pleurae (visceral and parietal) of each lung

The pleural cavity is the thin fluid-filled space between the two pulmonary pleurae of each lung. A pleura is a serous membrane which folds back onto itself to form a two-layered membranous pleural sac. The outer pleura is attached to the chest wall, but is separated from it by the endothoracic fascia. The inner pleura covers the lungs and adjoining structures, including blood vessels, bronchi and nerves. The pleural cavity can be viewed as a potential space because the two pleurae adhere to each other under all normal conditions. Parietal pleura projects up to 2.5 cm above the junction of the middle and medial third of the clavicle

The peritoneal cavity is a potential space between the parietal peritoneum and visceral peritoneum. Both the parietal and visceral peritonea are not different but the same peritoneum given two names depending on their function/location. It is one of the spaces derived from the coelomic cavity of the embryo, the others being the pleural cavities around the lungs and the pericardial cavity around the heart.

Liquid-based cytology

Liquid-based cytology is a method of preparing samples for examination in cytopathology. The sample is collected, normally by a small brush, in the same way as for a conventional smear test, but rather than the smear being transferred directly to a microscope slide, the sample is deposited into a small bottle of preservative liquid. At the laboratory the liquid is treated to remove other elements such as mucus before a layer of cells is placed on a slide. The technique allows more accurate results. The UK screening programmes changed their cervical screening method from the Pap test to liquid-based cytology in 2008.

Intervention cytology

Brushes used to collect samples for cytology. Journal.pone.0026395.g001 cervical cytology brushes.png
Brushes used to collect samples for cytology.

In interventional cytology the pathologist intervenes into the body for sample collection.

Fine-needle aspiration

Fine-needle aspiration, or fine-needle aspiration cytology (FNAC), involves use of a needle attached to a syringe is 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 be assisted by ultrasound 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 higher than when performed by a non-pathologist. [4] 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.

Hypodermic needle Device to inject substances into the circulatory system

A hypodermic needle, one of a category of medical tools which enter the skin, called sharps, is a very thin, hollow tube with a sharp tip that contains a small opening at the pointed end. It is commonly used with a syringe, a hand-operated device with a plunger, to inject substances into the body or extract fluids from the body. They are used to take liquid samples from the body, for example taking blood from a vein in venipuncture. Large bore hypodermic intervention is especially useful in catastrophic blood loss or treating shock.

Syringe a simple pump consisting of a plunger that fits tightly in a tube

A syringe is a simple reciprocating pump consisting of a plunger that fits tightly within a cylindrical tube called a barrel. The plunger can be linearly pulled and pushed along the inside of the tube, allowing the syringe to take in and expel liquid or gas through a discharge orifice at the front (open) end of the tube. The open end of the syringe may be fitted with a hypodermic needle, a nozzle or a tubing to help direct the flow into and out of the barrel. Syringes are frequently used in clinical medicine to administer injections, infuse intravenous therapy into the bloodstream, apply compounds such as glue or lubricant, and draw/measure liquids.

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.

FNAC has become synonymous to interventional cytology.

Sediment cytology

For cytology of sediment, 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.


The nucleus 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.

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:

Various normal functions of cell growth, metabolism, and division 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 examination and medical imaging. Cytology can be used to diagnose a condition and spare a patient from surgery to obtain a larger specimen. An example is thyroid FNAC; 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 may be dangerous to biopsy, such as pheochromocytoma. In general, a fine-needle aspiration can be done anywhere it is safe to put a needle, including liver, lung, kidney, and superficial masses.

Proper cytopathology technique takes time to master. Cytotechnologists and cytopathologists can assist clinicians by assisting with sample collection. A "quick read" is a peek under the microscope and can tell the clinician whether enough diagnostic material was obtained. Cytological specimens must be properly prepared so that the cells are not damaged.

Further information about the specimen may be gained by immunohistochemical stains and molecular testing, particularly 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 on a lymphoma specimen.

Body regions

Cytopathologic techniques are used in the examination of virtually all body organs and tissues:

See also

Notes and references

  1. Kirkpatrick; et al. (1989). The Cassell Concise English Dictionary. London. p. 324. ISBN   0-304-31806-X.
  2. Chapter 13, section of squamous cell carcinomas, in Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN   1-4160-2973-7.
  3. "Cytology". Collection development manual of the National Library of Medicine (4th ed.). Bethesda, MD: National Library of Medicine, National Institutes of Health, U.S. Department of Health and Human Services. 2004.
  4. Orell, S., et al. 2005. Fine Needle Aspiration Cytology. 4th Edition

Related Research Articles

Pap test screening test used to detect potentially pre-cancerous and cancerous processes in the endocervical canal

The Papanicolaou test is a method of cervical screening used to detect potentially precancerous and cancerous processes in the cervix. Abnormal findings are often followed up by more sensitive diagnostic procedures and if warranted, interventions that aim to prevent progression to cervical cancer. The test was independently invented by Dr. Georgios Papanikolaou and Dr. Aurel Babeș and named after Papanikolaou.

Anatomical pathology medical specialty

Anatomical pathology (Commonwealth) or Anatomic pathology (U.S.) is a medical specialty that is concerned with the diagnosis of disease based on the macroscopic, microscopic, biochemical, immunologic and molecular examination of organs and tissues. Over the last century, surgical pathology has evolved tremendously: from historical examination of whole bodies (autopsy) to a more modernized practice, centered on the diagnosis and prognosis of cancer to guide treatment decision-making in oncology. Its modern founder was the Italian scientist Giovan Battista Morgagni from Forlì.

Thyroid neoplasm

Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm, such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected than men. The estimated number of new cases of thyroid cancer in the United States in 2010 is 44,670 compared to only 1,690 deaths. Of all thyroid nodules discovered, only about 5 percent are cancerous, and under 3 percent of those result in fatalities.

Biopsy medical test involving sampling of cells or tissues for examination

A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist involving extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous and inflammatory conditions.


Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease. 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. In contrast, cytopathology examines (1) free cells or (2) tissue micro-fragments.

Fibroadenoma breast benign neoplasm comprised of fibrous and glandoular tissues located in breast

Fibroadenomas, are benign breast tumours characterized by an admixture of stromal and epithelial tissue. Breasts are made of lobules and ducts. These are surrounded by glandular, fibrous and fatty tissues. Fibroadenomas develop from the lobules. The glandular tissue and ducts grow over the lobule to form a solid lump.

Fine-needle aspiration diagnostic procedure to investigate lumps using a thin needle. can be either for histopathology or cytopathology

Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin, hollow needle is inserted into the mass for sampling of cells that, after being stained, will be examined under a microscope (biopsy). The sampling and biopsy considered together are called fine-needle aspiration biopsy (FNAB) or fine-needle aspiration cytology (FNAC). Fine-needle aspiration biopsies are very safe minor surgical procedures. Often, a major surgical biopsy can be avoided by performing a needle aspiration biopsy instead, eliminating the need for hospitalization. In 1981, the first fine-needle aspiration biopsy in the United States was done at Maimonides Medical Center. Today, this procedure is widely used in the diagnosis of cancer and inflammatory conditions.

Papanicolaou stain

Papanicolaou stain is a multichromatic staining cytological technique developed by George Papanikolaou, the father of cytopathology.

Surgical pathology most significant and time-consuming area of practice for most anatomical pathologists

Surgical pathology is the most significant and time-consuming area of practice for most anatomical pathologists. Surgical pathology involves gross and microscopic examination of surgical specimens, as well as biopsies submitted by surgeons and non-surgeons such as general internists, medical subspecialists, dermatologists, and interventional radiologists.

Cytotechnology is the microscopic interpretation of cells to detect cancer and other abnormalities. This includes the examination of samples collected from the uterine cervix, lung, gastrointestinal tract or body cavities.

Thyroid nodule human disease

Thyroid nodules are nodules which commonly arise within an otherwise normal thyroid gland. They may be hyperplasia or a thyroid neoplasm, but only a small percentage of the latter are thyroid cancers. Small, asymptomatic nodules are common, and many people who have them are unaware of them. But nodules that grow larger or produce symptoms may eventually need medical care. Goitres may have one nodule – uninodular, multiple nodules – multinodular, or be diffuse.

Skin biopsy is a biopsy technique in which a skin lesion is removed to be sent to a pathologist to render a microscopic diagnosis. It is usually done under local anesthetic in a physician's office, and results are often available in 4 to 10 days. It is commonly performed by dermatologists. Skin biopsies are also done by family physicians, internists, surgeons, and other specialties. However, performed incorrectly, and without appropriate clinical information, a pathologist's interpretation of a skin biopsy can be severely limited, and therefore doctors and patients may forgo traditional biopsy techniques and instead choose Mohs surgery. There are four main types of skin biopsies: shave biopsy, punch biopsy, excisional biopsy, and incisional biopsy. The choice of the different skin biopsies is dependent on the suspected diagnosis of the skin lesion. Like most biopsies, patient consent and anesthesia are prerequisites.

Many types of skin tumors, both benign (noncancerous) and malignant (cancerous), exist. Approximately 20-40% of primary skin tumors are malignant in dogs and 50-65% are malignant in cats. Not all forms of skin cancer in cats and dogs are caused by sun exposure, but it can happen occasionally. On dogs, the nose and pads of the feet contain sensitive skin and no fur to protect from the sun. Also, cats and dogs with thin or light-colored coats are at a higher risk of sun damage over their entire bodies.

Lobular carcinoma in situ Human disease

Lobular carcinoma in situ (LCIS) is an incidental microscopic finding with characteristic cellular morphology and multifocal tissue patterns. The condition is a laboratory diagnosis and refers to unusual cells in the lobules of the breast. The lobules and acini of the terminal duct-lobular unit (TDLU), the basic functional unit of the breast, may become distorted and undergo expansion due to the abnormal proliferation of cells comprising the structure. These changes represent a spectrum of atypical epithelial lesions that are broadly referred to as lobular neoplasia (LN).

High-grade prostatic intraepithelial neoplasia

High-grade prostatic intraepithelial neoplasia (HGPIN) is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma.

The Bethesda system (TBS) is a system for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap smear results. It was introduced in 1988 and revised in 1991, 2001, and 2014. The name comes from the location of the conference that established the system.

FNA Mapping is an application of fine-needle aspiration (FNA) to the testis for the diagnosis of male infertility. FNA cytology has been used to examine pathological human tissue from various organs for over 100 years. As an alternative to open testicular biopsy for the last 40 years, FNA Mapping has helped to characterize states of human male infertility due to defective spermatogenesis. Although recognized as a reliable, and informative technique, testis FNA has not been widely used in U.S. to evaluate male infertility. Recently however, testicular FNA has gained popularity as both a diagnostic and therapeutic tool for the management of clinical male infertility for several reasons:

  1. The testis is an ideal organ for evaluation by FNA because of its uniform cellularity and easy accessibility.
  2. The trend toward minimally invasive procedures and cost-containment views FNA favorably compared to surgical testis biopsy.
  3. The realization that the specific histologic abnormality observed on testis biopsy has no definite correlation to either the etiology of infertility or to the ability to find sperm for assisted reproduction.
  4. Assisted reproduction has undergone dramatic advances such that testis sperm are routinely used for biological pregnancies, thus fueling the development of novel FNA techniques to both locate and procure sperm.
Breast biopsy

A breast biopsy is usually done after a suspicious lesion is discovered on either Mammography or Ultrasound in order to get tissue for pathological diagnosis. Several methods for a breast biopsy now exist. The most appropriate method of biopsy for a patient depends upon a variety of factors, including the size, location, appearance and characteristics of the abnormality. The different types of breast biopsies include fine needle aspiration (FNA), vacuum assisted biopsy, core needle biopsy, and surgical excision biopsy. Breast biopsies can be done under ultrasound, MRI or a Stereotactic biopsy technique. Vacuum assisted biopsies are typically done using stereotactic techniques when the suspicious lesion can only be seen on mammography. On average, 5-10 biopsies of a suspicious breast lesion will lead to the diagnosis of one case of breast cancer.

Sampling (medicine) collection of matter for medical purposes

In medicine, sampling is gathering of matter from the body to aid in the process of a medical diagnosis and/or evaluation of an indication for treatment, further medical tests or other procedures. In this sense, the sample is the gathered matter, and the sampling tool or sampler is the person or material to collect the sample.