Carcinoma


Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal or ectodermal germ layer during embryogenesis.
Carcinomas occur when the DNA of a cell is damaged or altered and the cell begins to grow uncontrollably and become malignant. It is from the translit=karkinoma.

Classification

As of 2004, no simple and comprehensive classification system has been devised and accepted within the scientific community. Traditionally, however, malignancies have generally been classified into various types using a combination of criteria, including:
The cell type from which they start; specifically:
Other criteria that play a role include:
; Adenocarcinoma: 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.
; 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 with 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, giant cell carcinoma, and sarcomatoid 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. Very rarely, tumors may contain individual components resembling both carcinoma and true sarcoma, including carcinosarcoma and pulmonary blastoma. A history of cigarette smoking is the most common cause of large cell carcinoma.

Carcinoma of unknown primary site

The term carcinoma has also come to encompass malignant tumors composed of transformed cells whose origin or developmental lineage is unknown, 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.

ICD-10 code

The term carcinoma in situ is a term for cells that are significantly abnormal but not cancer. They are thus not typically carcinomas.

Pathogenesis

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 displaying a number of abnormal, malignant cellular properties that, when taken together, are considered characteristic of cancer, including:
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.
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.

Invasion and metastasis

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.

Mutation

has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans is about 70 new mutations per generation.
Carcinomas, however, have much higher mutation frequencies. The particular frequency depends on tissue type, whether a mis-match DNA repair deficiency is present, and exposure to DNA damaging agents such as components of tobacco smoke. Tuna and Amos have summarized the mutation frequencies per megabase in some carcinomas, as shown in the table.

Cause of mutations

The likely major underlying cause of mutations in carcinomas is DNA damage. For example, in the case of lung cancer, DNA damage is caused by agents in exogenous genotoxic tobacco smoke. Endogenous DNA damage is also very frequent, occurring on average more than 60,000 times a day in the genomes of human cells. Externally and endogenously caused damages may be converted into mutations by inaccurate translesion synthesis or inaccurate DNA repair.
High frequency
The high frequency of mutations in the total genome within carcinomas suggests that, often, an early carcinogenic alteration may be a deficiency in DNA repair. For instance, mutation rates substantially increase in cells defective in DNA mismatch repair
A deficiency in DNA repair, itself, can allow DNA damages to accumulate, and error-prone translesion synthesis past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to epigenetic alterations or epimutations. While a mutation or epimutation in a DNA repair gene, itself, would not confer a selective advantage, such a repair defect may be carried along as a passenger in a cell when the cell acquires an additional mutation/epimutation that does provide a proliferative advantage. Such cells, with both proliferative advantages and one or more DNA repair defects, likely give rise to the high frequency of total genome mutations seen in carcinomas.

DNA repair

In somatic cells, deficiencies in DNA repair sometimes arise by mutations in DNA repair genes, but much more often are due to epigenetic reductions in expression of DNA repair genes. Thus, in a sequence of 113 colorectal carcinomas, only four had somatic missense mutations in the DNA repair gene MGMT, while the majority of these cancers had reduced MGMT protein expression due to methylation of the MGMT promoter region.

Diagnosis

Carcinomas can be definitively diagnosed through biopsy, including fine-needle aspiration, 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

Some carcinomas are named for their or the putative cell of origin,.

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 more recent staging systems, substages 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 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:
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.

Epidemiology

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. Less than 1% of carcinoma diagnoses are in children.
The two biggest risk factors for ovarian carcinoma are age and family history.