Carcinoma
Encyclopedia
Carcinoma is the medical term for the most common type of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endoderm
Endoderm
Endoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the ectoderm and mesoderm , with the endoderm as the intermost layer...

al or ectoderm
Ectoderm
The "ectoderm" is one of the three primary germ cell layers in the very early embryo. The other two layers are the mesoderm and endoderm , with the ectoderm as the most exterior layer...

al germ layer during embryogenesis
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...

. More specifically, a carcinoma is tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 tissue
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...

 derived from putative epithelial cells
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

 whose genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

 has become altered or damaged to such an extent that the cells become transformed, and begin to exhibit abnormal malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...

 properties.

Carcinoma of unknown primary (CUP)

The term carcinoma has also come to encompass malignant tumors composed of transformed cells
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....

 whose origin or developmental lineage is unknown (see CUP
Cancer of unknown primary origin
Cancer of unknown primary origin is the diagnosis when metastatic cancer is found but the place where the cancer began cannot be determined. About two to four percent of all cancer patients have a cancer whose primary site is never identified...

), but that possess certain specific molecular, cellular, and histological characteristics typical of epithelial cells. This may include the production of one or more forms of cytokeratin
Cytokeratin
Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue. The term "cytokeratin" began to be used in the late 1970s when the protein subunits of keratin intermediate filaments inside cells were first being identified and...

 or other intermediate filaments, intercellular bridge structures, keratin
Keratin
Keratin refers to a family of fibrous structural proteins. Keratin is the key of structural material making up the outer layer of human skin. It is also the key structural component of hair and nails...

 pearls, and/or tissue architectural motifs such as stratification or pseudo-stratification.

Pathogenesis of cancer

Cancer occurs when a single progenitor cell accumulates mutations and other changes in the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

, histones, and other biochemical compounds that make up the cell's genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

. The cell genome controls the structure of the cell's biochemical components, the biochemical reactions that occur within the cell, and the biological interactions of that cell with other cells. Certain combinations of mutations in the given progenitor cell ultimately result in that cell (also called a cancer stem cell) displaying a number of abnormal, malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...

 cellular properties that, when taken together, are considered characteristic of cancer, including:
  • the ability to continue to divide perpetually, producing an exponentially (or near-exponentially) increasing number of new malignant cancerous "daughter cells" (uncontrolled mitosis
    Mitosis
    Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

    );
  • the ability to penetrate normal body surfaces and barriers, and to bore into or through nearby body structures and tissues (local invasiveness);
  • the ability to spread to other sites within the body (metastasize
    Metastasis
    Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

    ) by penetrating or entering into the lymphatic vessels (regional metastasis) and/or the blood vessels (distant metastasis).


If this process of continuous growth, local invasion, and regional and distant metastasis is not halted via a combination of stimulation of immunological defenses and medical treatment interventions, the end result is that the host suffers a continuously increasing burden of tumor cells throughout the body. Eventually, the tumor burden increasingly interferes with normal biochemical functions carried out by the host's organs, and death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

 ultimately ensues.

Pathogenesis of carcinoma

Carcinoma is but one form of cancer - one composed of cells that have developed the cytological appearance, histological architecture, or molecular characteristics of epithelial cells. A progenitor carcinoma stem cell can be formed from any of a number of oncogenic combinations of mutations in a totipotent cell, a multipotent cell,or a mature differentiated cell.

Epidemiology of carcinoma

  • Demography (Age, Race, Gender, etc.)


While cancer is generally considered a disease of old age, children can also develop cancer. In contrast to adults, carcinomas are exceptionally rare in children..
  • Causes

Smoking, environment, etc.

Carcinoma in situ

The term Carcinoma in situ
Carcinoma in situ
Carcinoma in situ is an early form of cancer that is defined by the absence of invasion of tumor cells into the surrounding tissue, usually before penetration through the basement membrane. In other words, the neoplastic cells proliferate in their normal habitat, hence the name "in situ"...

 (or CIS) refers to a small, localized carcinoma that has not yet invaded through the epithelial basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...

 delimiting the carcinomatous cells from adjacent normal cells. CIS is a pre-invasive cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

, and not a pre-malignant entity.

Nearly all cases of CIS will continue to grow and progress until they begin to infiltrate and penetrate into and through the basal membrane or other/adjacent structures. Once invasion occurs, they are no longer considered CIS lesions, but truly invasive carcinomas. If the lesion
Lesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...

 can be completely removed via surgical resection
Segmental resection
Segmental resection is a surgical procedure to remove part of an organ or gland. It may also be used to remove a tumor and normal tissue around it. In lung cancer surgery, segmental resection refers to removing a section of a lobe of the lung.- External links :* entry in the public domain NCI...

, cryotherapy
Cryotherapy
Cryotherapy is the local or general use of low temperatures in medical therapy or the removal of heat from a body part. The term "cryotherapy" comes from the Greek cryo meaning cold and the word therapy meaning cure...

, laser ablation
Laser ablation
Laser ablation is the process of removing material from a solid surface by irradiating it with a laser beam. At low laser flux, the material is heated by the absorbed laser energy and evaporates or sublimates. At high laser flux, the material is typically converted to a plasma...

, or some other locally-targeted treatment modality before frank invasion and metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 develops, cure rates for CIS approach 100%.

In some cases, CIS lesions may gradually re-assume more normal-looking cytological and histological characteristics, thereby becoming lower-grade neoplasms. Biologically, this can very often result in less aggressive, slower-growing neoplasms. Indeed, the appearance of the component cells and local tissue architecture at the local site of the CIS may eventually normalize to the point where the transformed cells no longer meet the consensus requirements necessary for it to be classified as a carcinoma. Therefore, this abnormality would no longer qualify as a true cancer.

These changes are also usually accompanied by decreases in surface area and/or volume of the abnormal area. In some not-insignificant proportion of cases, the abnormal cells/tissue may disappear entirely, with the resulting local area containing only normal-appearing tissue. The process is often referred to by oncologists and pathologists as regression
Regression
Regression could refer to:* Regression , a defensive reaction to some unaccepted impulses* Regression analysis, a statistical technique for estimating the relationships among variables...

 of the CIS lesion. Regression of CIS effectively results in the progressive conversion of a malignant neoplasm to a benign one, to a localized area of normal or near-normal tissue, with or without associated scar tissue, which often forms secondary to apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

, necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

, and fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...

.

Regression is most often manifested after exposure to prolonged changes in the quality and intensity of environmental and/or immunological stimuli.

A very common example is the regression in some lesions of CIS located in the main central and segmental bronchi of the lung. Many pre-invasive lesions in cases of squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...

 often regress after long-term reduced exposure of the affected cells and tissues to the original environmental carcinogenic stimulus, such as that seen after long-term abstention from tobacco smoking. Another relatively common example is the immunologically-driven clearing of Human Papilloma Virus HPV from transformed epithelial cells of the uterine
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...

 cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...

, which results in regression of cervical CIS lesions.

Classification of carcinomas

Malignant neoplasms are exceptionally heterogeneous entities, reflecting the wide variety, intensity, and potency of various carcinogenic promoters.

To date, no simple and comprehensive method for classifying them has yet been devised and accepted within the scientific community.

Traditionally, however, malignancies have generally been classified into various taxa using a combination of criteria, including:

One commonly used classification scheme classifies these major cancer types on the basis of cell genesis, specifically:
  1. Their (putative) cell (or cells) of origin
    1. Epithelial cells => carcinoma
    2. Non-hematopoietic mesenchymal cells => sarcoma
      Sarcoma
      A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...

    3. Hematopoietic cells
      1. bone marrow
        Bone marrow
        Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

        -derived cells that normally mature in the bloodstream => Leukemia
        Leukemia
        Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

      2. bone marrow-derived cells that normally mature in the lymphatic system => Lymphoma
        Lymphoma
        Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...

    4. Germ cells => Germinoma
      Germinoma
      A germinoma is a type of germ cell tumor which is not differentiated upon examination. It may be benign or malignant.-Classification:The term germinoma most often has referred to a tumor in the brain that has a histology identical to two other tumors: dysgerminoma in the ovary and seminoma in the...



Other criteria that play a role in a cancer diagnosis include:
  • The degree to which the malignant cells resemble their normal, untransformed counterparts
  • the appearance of the local tissue and stromal architecture
  • the anatomical location from which tumors arise
  • genetic, epigenetic, and molecular features

Histological types and variants of carcinoma

Adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...

: Refers to a carcinoma featuring microscopic glandular-related tissue cytology, tissue architecture, and/or gland-related molecular products, e.g., mucin
Mucin
Mucins are a family of high molecular weight, heavily glycosylated proteins produced by epithelial tissues in most metazoans. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell...

.
Squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...

:
Refers to a carcinoma with observable features and characteristics indicative of squamous differentiation (intercellular bridges, keratinization, squamous pearls).

Adenosquamous carcinoma
Adenosquamous carcinoma
Adenosquamous carcinoma is a type of cancer that contains two types of cells: squamous cells and gland-like cells.- External links :* entry in the public domain NCI Dictionary of Cancer Terms...

:
Refers to a mixed tumor containing both adenocarcinoma and squamous cell carcinoma, wherein each of these cell types comprise at least 10% of the tumor volume.

Anaplastic
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...

 carcinoma:
Refers to a heterogeneous group of high-grade carcinomas that feature cells lacking distinct histological or cytological evidence of any of the more specifically differentiated neoplasms. These tumors are referred to as Anaplastic or Undifferentiated
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...

 carcinomas.

Large cell carcinoma
Large cell carcinoma
Large-cell lung carcinoma is a heterogeneous group of undifferentiated malignant neoplasms originating from transformed epithelial cells in the lung.-Incidence:In most series, LCLC's comprise between 5% and 10% of all lung cancers....

Composed of large, monotonous rounded or overtly polygonal-shaped cells with abundant cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

.

Small cell carcinoma
Small cell carcinoma
Small cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix and prostate....

Cells are usually round and are less than approximately 3 times the diameter of a resting lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...

 and little evident cytoplasm. Occasionally, small cell malignancies may themselves have significant components of slightly polygonal and/or spindle-shaped cells.


There are a large number of rare subtypes of anaplastic, undifferentiated carcinoma. Some of the more well known include the lesions containing pseudo-sarcomatous
Sarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...

 components: spindle cell carcinoma (containing elongated cells resembling connective tissue cancers), giant cell carcinoma (containing huge, bizarre, multinucleated cells), and sarcomatoid carcinoma
Sarcomatoid carcinoma
Sarcomatoid carcinoma is a relatively uncommon form of cancer whose malignant cells have histological, cytological, or molecular properties of both epithelial tumors and mesenchymal tumors .-Sarcomatoid Carcinomas of the Lung:...

 (mixtures of spindle and giant cell carcinoma). Pleomorphic carcinoma contains spindle cell and/or giant cell components, plus at least a 10% component of cells characteristic of more highly differentiated types (i.e. adenocarcinoma and/or squamous cell carcinoma). Very rarely, tumors may contain individuals components resembling both carcinoma and true sarcoma
Sarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...

, including carcinosarcoma
Carcinosarcoma
Carcinosarcoma is a malignant tumor that is a mixture of carcinoma and sarcoma ....

 and pulmonary blastoma.

Frequent organ sites of carcinoma

  • Lung: Carcinoma comprises >98% of all lung cancer
    Lung cancer
    Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

    s.
  • Breast: Nearly all breast cancers are ductal carcinoma
    Ductal carcinoma
    Mammary ductal carcinoma is the most common type of breast cancer in women. It comes in two forms: invasive ductal carcinoma , an infiltrating, malignant and abnormal proliferation of neoplastic cells in the breast tissue, or ductal carcinoma in situ , a noninvasive, possibly malignant, neoplasm...

    .
  • Prostate: The most common form of carcinoma of the prostate
    Prostate cancer
    Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

     is adenocarcinoma.
  • Colon and rectum: Nearly all malignancies of the colon and rectum are either adenocarcinoma or squamous cell carcinoma.
  • Pancreas: Pancreatic carcinoma is almost always of the adenocarcinoma type and is highly lethal.


Some carcinomas are named for their or the putative cell of origin, (e.g.(hepatocellular carcinoma
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...

, renal cell carcinoma
Renal cell carcinoma
Renal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases...

.

Invasion and metastasis of carcinomas

The hallmark of a malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...

 tumor is its tendency to invade and infiltrate local and adjacent structures and, eventually, spread from the site of its origin to non-adjacent regional and distant sites in the body, a process called metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

. If unchecked, tumor growth and metastasis eventually creates a tumor burden so great that the host succumbs. Carcinoma metastasizes through both the lymph nodes and the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

.

Diagnosis

Carcinomas can be definitively diagnosed through biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject 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...

, including fine-needle aspiration (FNA), core biopsy, or subtotal removal of single node,. Microscopic examination by a pathologist is then necessary to identify molecular, cellular, or tissue architectural characteristics of epithelial cells.

Types of carcinoma (by ICD-O code)

  • (8010-8045) Epithelial neoplasms, NOS
  • (8050-8080) Squamous cell neoplasms
    • Squamous cell carcinoma
      Squamous cell carcinoma
      Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...

      , NOS
  • (8090-8110) Basal cell neoplasms
    • Basal cell carcinoma
      Basal cell carcinoma
      Basal-cell carcinoma is the most common type of skin cancer. It rarely metastasizes or kills. However, because it can cause significant destruction and disfigurement by invading surrounding tissues, it is still considered malignant. Statistically, approximately 3 out of 10 Caucasians may develop a...

      , NOS
  • (8120-8130) Transitional cell carcinomas
  • (8140-8380) Adenocarcinomas
    • Adenocarcinoma
      Adenocarcinoma
      Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...

      , NOS
    • Linitis plastica
      Linitis plastica
      Linitis plastica, also known as Brinton's disease or leather bottle stomach, is a morphological variant of diffuse stomach cancer....

    • Vipoma
      VIPoma
      A VIPoma is a rare endocrine tumor, usually originating in the pancreas, that produces vasoactive intestinal peptide ....

    • Cholangiocarcinoma
      Cholangiocarcinoma
      Cholangiocarcinoma is a cancer of the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater...

    • Hepatocellular carcinoma
      Hepatocellular carcinoma
      Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...

      , NOS
    • Adenoid cystic carcinoma
      Adenoid cystic carcinoma
      Adenoid cystic cancer is a rare type of cancer that can exist in many different body sites. It most often occurs in the areas of the head and neck, in particular the salivary glands; but has also been reported in the breast, lacrimal gland of the eye, lung, brain, bartholin gland, trachea, and...

    • Renal cell carcinoma
      Renal cell carcinoma
      Renal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases...

    • Grawitz tumor
  • (8390-8420) Adnexal and Skin appendage
    Skin appendage
    Skin appendages are appendages that are associated with the skin and serve a particular function. In humans some of the more common skin appendages are hairs , arrector pilli , sebaceous glands , sweat glands Skin appendages are appendages that are associated with the skin and serve a particular...

     Neoplasms
  • (8430-8439) Mucoepidermoid Neoplasms
  • (8440-8490) Cystic, Mucinous and Serous Neoplasms
  • (8500-8540) Ductal, Lobular and Medullary
    Renal medulla
    The renal medulla is the innermost part of the kidney. The renal medulla is split up into a number of sections, known as the renal pyramids. Blood enters into the kidney via the renal artery, which then splits up to form the arcuate arterioles. The arcuate arterioles each in turn branch into...

     Neoplasms
  • (8550-8559) Acinar cell
    Acinus
    An acinus refers to any cluster of cells that resembles a many-lobed "berry," such as a raspberry...

     neoplasms
  • (8560-8580) Complex epithelial neoplasms

Staging

Staging
Staging
Staging may refer to:* Staging , a chef works briefly and without pay in another chef's kitchen to learn to new techniques and cuisines* Staging , the use of multiple engines and propellant to launch a rocket...

 of carcinoma refers to the process of combining physical/clinical examination, pathological review of cells and tissues, surgical techniques, laboratory tests, and imaging studies in a logical fashion to obtain information about the size of the neoplasm and the extent of its invasion and metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

.

Carcinomas are usually staged with Roman numerals. In most classifications, Stage I and Stage II carcinomas are confirmed when the tumor has been found to be small and/or to have spread to local structures only. Stage III carcinomas typically have been found to have spread to regional lymph nodes, tissues, and/or organ structures, while Stage IV tumors have already metastasized through the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

 to distant sites, tissues, or organs.

In some types of carcinomas, Stage 0 carcinoma has been used to describe carcinoma in situ
Carcinoma in situ
Carcinoma in situ is an early form of cancer that is defined by the absence of invasion of tumor cells into the surrounding tissue, usually before penetration through the basement membrane. In other words, the neoplastic cells proliferate in their normal habitat, hence the name "in situ"...

, and occult
Occult
The word occult comes from the Latin word occultus , referring to "knowledge of the hidden". In the medical sense it is used to refer to a structure or process that is hidden, e.g...

 carcinomas detectable only via examination of sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....

) for malignant cells (in lung carcinomas
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

).

In more recent staging systems, substages (a, b, c) are becoming more commonly used to better define groups of patients with similar prognosis or treatment options.

Carcinoma stage is the variable that has been most consistently and tightly linked to the prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...

 of the malignancy.

The criteria for staging can differ dramatically based upon the organ system in which the tumor arises. For example, the colon and bladder cancer staging system relies on depth of invasion, staging of breast carcinoma is more dependent on the size of the tumor, and in renal carcinoma, staging is based on both the size of the tumor and the depth of the tumor invasion into the renal sinus. Carcinoma of the lung has a more complicated staging system, taking into account a number of size and anatomic variables.

The UICC/AJCC TNM systems are most often used. http://www.cancerstaging.org/mission/whatis.html For some common tumors, however, classical staging methods (such as the Dukes classification for colon cancer) are still used.

Grading

Grading of carcinomas refers to the employment of criteria intended to semi-quantify the degree of cellular and tissue maturity seen in the transformed cells relative to the appearance of the normal parent epithelial tissue from which the carcinoma derives.

Grading of carcinoma is most often done after a treating physician and/or surgeon obtains a sample of suspected tumor tissue using surgical resection, needle or surgical biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject 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...

, direct washing or brushing of tumor tissue, sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....

 cytopathology
Cytopathology
Cytopathology is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by Rudolf Virchow in 1858. A common application of cytopathology is the Pap smear, used as a screening tool, to detect precancerous cervical lesions and prevent cervical...

, etc. A pathologist then examines the tumor and its stroma
Stroma (animal tissue)
In animal tissue, stroma refers to the connective, supportive framework of a biological cell, tissue, or organ.The stroma in animal tissue is contrasted with the parenchyma.Examples include:* Stroma of iris...

, perhaps utilizing staining, immunohistochemistry
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...

, 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...

, or other methods. Finally, the pathologist classifies the tumor semi-quantitatively into one of three or four grades, including:
  • Grade 1, or well differentiated: there is a close, or very close, resemblance to the normal parent tissue, and the tumor cells are easily identified and classified as a particular malignant histological entity;
  • Grade 2, or moderately differentiated: there is considerable resemblance to the parent cells and tissues, but abnormalities can commonly be seen and the more complex features are not particularly well-formed;
  • Grade 3, or poorly differentiated: there is very little resemblance between the malignant tissue and the normal parent tissue, abnormalities are evident, and the more complex architectural features are usually rudimentary or primitive;
  • Grade 4, or undifferentiated carcinoma: these carcinomas bear no significant resemblance to the corresponding parent cells and tissues, with no visible formation of glands, ducts, bridges, stratified layers, keratin pearls, or other notable characteristics consistent with a more highly differentiated neoplasm.


Although there is definite and convincing statistical correlation
Correlation
In statistics, dependence refers to any statistical relationship between two random variables or two sets of data. Correlation refers to any of a broad class of statistical relationships involving dependence....

between carcinoma grade and tumor prognosis for some tumor types and sites of origin, the strength of this association can be highly variable. It may be stated generally, however, that the higher the grade of the lesion, the worse is its prognosis.
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