Carcinoma

Carcinoma (Gk. karkinos, or "crab", and -oma, "growth") is the medical term for the most common type of cancer 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 endodermal or ectodermal germ layer during embryogenesis. More specifically, a carcinoma is tumor tissue derived from putative epithelial cells whose genome has become altered or damaged to such an extent that the cells become transformed, and begin to exhibit abnormal malignant properties.

Carcinoma of unknown primary (CUP)
The term carcinoma has also come to encompass malignant tumors composed of transformed cells whose origin or developmental lineage is unknown (see CUP), 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 or other intermediate filaments, intercellular bridge structures, keratin 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, histones, and other biochemical compounds that make up the cell's genome. 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 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);
 * 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) 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 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, Sex, 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..

Smoking, environment, etc.
 * Causes

Carcinoma In situ
The term carcinoma in situ (or CIS) refers to a small, localized carcinoma that has not yet invaded through the epithelial basement membrane delimiting the carcinomatous cells from adjacent normal cells. CIS is a pre-invasive cancer, 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 can be completely removed via surgical resection, cryotherapy, laser ablation, or some other locally-targeted treatment modality before frank invasion and metastasis 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 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, necrosis, and fibrosis.

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 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 cervix, 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
 * 2) Epithelial cells => carcinoma
 * 3) Non-hematopoietic mesenchymal cells => sarcoma
 * 4) Hematopoietic cells
 * 5) bone marrow-derived cells that normally mature in the bloodstream => Leukemia
 * 6) bone marrow-derived cells that normally mature in the lymphatic system => Lymphoma
 * 7) Germ cells => Germinoma

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:
 * (adeno = gland) Refers to a carcinoma featuring microscopic glandular-related tissue cytology, tissue architecture, and/or gland-related molecular products, e.g., mucin.


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


 * Adenosquamous carcinoma:
 * 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 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 carcinomas.


 * Large cell carcinoma
 * Composed of large, monotonous rounded or overtly polygonal-shaped cells with abundant cytoplasm.


 * Small cell carcinoma
 * Cells are usually round and are less than approximately 3 times the diameter of a resting lymphocyte 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 components: spindle cell carcinoma (containing elongated cells resembling connective tissue cancers), giant cell carcinoma (containing huge, bizarre, multinucleated cells), and sarcomatoid carcinoma (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, including carcinosarcoma and pulmonary blastoma.

Frequent organ sites of carcinoma

 * Lung: Carcinoma comprises >98% of all lung cancers.
 * Breast: Nearly all breast cancers are ductal carcinoma.
 * Prostate: The most common form of carcinoma of the prostate 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, renal cell carcinoma).

Invasion and metastasis of carcinomas
The hallmark of a malignant 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. 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.

Diagnosis
Carcinomas can be definitively diagnosed through biopsy, 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, NOS
 * (8090-8110) Basal cell neoplasms
 * Basal cell carcinoma, NOS
 * (8120-8130) Transitional cell carcinomas
 * (8140-8380) Adenocarcinomas
 * Adenocarcinoma, NOS
 * Linitis plastica
 * Vipoma
 * Cholangiocarcinoma
 * Hepatocellular carcinoma, NOS
 * Adenoid cystic carcinoma
 * Renal cell carcinoma
 * Grawitz tumor
 * (8390-8420) Adnexal and Skin appendage Neoplasms
 * (8430-8439) Mucoepidermoid Neoplasms
 * (8440-8490) Cystic, Mucinous and Serous Neoplasms
 * (8500-8540) Ductal, Lobular and Medullary Neoplasms
 * (8550-8559) Acinar cell neoplasms
 * (8560-8580) Complex epithelial neoplasms

Staging
Staging 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.

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 to distant sites, tissues, or organs.

In some types of carcinomas, Stage 0 carcinoma has been used to describe carcinoma in situ, and occult carcinomas detectable only via examination of sputum for malignant cells (in lung carcinomas).

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 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. 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, direct washing or brushing of tumor tissue, sputum cytopathology, etc. A pathologist then examines the tumor and its stroma, perhaps utilizing staining, immunohistochemistry, flow cytometry, 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 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.