Carcinoma

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Carcinoma
Small cell lung cancer - cytology.jpg
Micrograph of a lung primary small cell carcinoma, a type of carcinoma. The clustered cancerous cells consist primarily of nucleus (purple); they have only a scant rim of cytoplasm. The surrounding pale staining, discoid cells are red blood cells. Cytopathology specimen. Field stain.
Specialty Oncology

Carcinoma is a category of types of cancer that develop from epithelial cells. [1] 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 [2] or ectodermal germ layer during embryogenesis. [3]

Cancer disease of uncontrolled, unregulated and abnormal cell growth

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss and a change in bowel movements. While these symptoms may indicate cancer, they may have other causes. Over 100 types of cancers affect humans.

Endoderm

Endoderm is one of the three primary germ layers in the very early embryo. The other two layers are the ectoderm and mesoderm, with the endoderm being the innermost layer. Cells migrating inward along the archenteron form the inner layer of the gastrula, which develops into the endoderm.

Mesoderm

In all bilaterian animals, the mesoderm is one of the three primary germ layers in the very early embryo. The other two layers are the ectoderm and endoderm, with the mesoderm as the middle layer between them.

Contents

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 Greek, καρκίνωμα, karkinoma, meaning sore, ulcer, or cancer (itself derived from karkinos meaning crab). [4]

DNA Molecule that encodes the genetic instructions used in the development and functioning of all known organisms and many viruses

Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids; alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.

Classification

As of 2004, no simple and comprehensive classification system has been devised and accepted within the scientific community. [5] Traditionally, however, malignancies have generally been classified into various types using a combination of criteria, including: [6]

The cell type from which they start; specifically:

Sarcoma cell type cancer that has material basis in abnormally proliferating cells derived from embryonic mesoderm

A sarcoma is a cancer that arises from transformed cells of mesenchymal origin. Thus, malignant tumors made of cancellous bone, cartilage, fat, muscle, vascular, or hematopoietic tissues are, by definition, considered sarcomas. This is in contrast to a malignant tumor originating from epithelial cells, which are termed carcinoma. Human sarcomas are quite rare. Common malignancies, such as breast, colon, and lung cancer, are almost always carcinoma. The term is from the Greek σάρξ sarx meaning "flesh".

Bone marrow is a semi-solid tissue which may be found within the spongy or cancellous portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production or hematopoiesis. It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. On average, bone marrow constitutes 4% of the total body mass of humans; in an adult having 65 kilograms of mass, bone marrow typically accounts for approximately 2.6 kilograms (5.7 lb).

Leukemia group of cancers that usually begin in the bone marrow

Leukemia, also spelled leukaemia, that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called blasts or leukemia cells. Symptoms may include bleeding and bruising problems, feeling tired, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy.

Other criteria that play a role in a cancer diagnosis include:

Histological types

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 with little evident cytoplasm. Occasionally, small cell malignancies may themselves have significant components of slightly polygonal and/or spindle-shaped cells. [7]

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. [7] A history of cigarette smoking is the most common cause of large cell carcinoma.

Spindle cell carcinoma is a type of cancer that begins in the skin or in tissues that line or cover internal organs and that contains long spindle-shaped cells. It is also called 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 ("carcinoma") and mesenchymal tumors ("sarcoma").

Carcinosarcoma mixed cell type cancer that has material basis in carcinomatous (epithelial tissue) and sarcomatous (connective tissue) components

Carcinosarcomas are malignant tumors that consist of a mixture of carcinoma and sarcoma. Carcinosarcomas are rare tumors, and can arise in diverse organs, such as the skin, salivary glands, lungs, the esophagus, pancreas, colon, uterus and ovaries.

Carcinoma of unknown primary

The term carcinoma has also come to encompass malignant tumors composed of transformed cells whose origin or developmental lineage is unknown (see cancer of unknown primary origin; 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. [5] [6]

ICD-10 code

Carcinoma In situ

The term carcinoma in situ (or CIS) is a term for cells that are significantly abnormal but not cancer. [8] They are thus not typically carcinomas. [9]

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 (also called a cancer stem 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. [5] [6] A progenitor carcinoma stem cell can be formed from any of a number of oncogenic combinations of mutations in a totipotent cell,[ citation needed ] a multipotent cell,[ citation needed ] or a mature differentiated cell.[ citation needed ]

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

Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation. [11]

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 (Mb) in some carcinomas, [12] as shown in the table (along with the indicated frequencies of mutations per genome).

The high mutation frequencies in carcinomas reflect the genome instability characteristic of cancers.[ citation needed ]

Mutation frequencies
Cell typeMutation frequency
Per megabasePer dipload genome
Germline0.02370
Prostate cancer0.95,400
Colorectal carcinoma~5~30,000
Microsatellite stable (MSS) colon cancer2.816,800
Microsatellite instable (MSI) colon cancer (mismatch repair deficient)47282,000
Hepatocellular carcinoma4.225,200
Breast cancer1.18–1.667,080–9,960
Lung cancer17.7106,200
Small cell lung cancer7.444,400
Non-small cell lung cancer (smokers)10.563,000
Non-small cell lung cancer (never-smokers)0.63,600
Lung adenocarcinoma (smokers)9.858,500
Lung adenocarcinoma (never-smokers)1.710,200

Cause of mutations

The likely major underlying cause of mutations in carcinomas is DNA damage. [13] For example, in the case of lung cancer, DNA damage is caused by agents in exogenous genotoxic tobacco smoke (e.g. acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide and isoprene). [14] Endogenous (metabolically-caused) DNA damage is also very frequent, occurring on average more than 60,000 times a day in the genomes of human cells [13] (also see DNA damage (naturally occurring)). Externally and endogenously caused damages may be converted into mutations by inaccurate translesion synthesis or inaccurate DNA repair (e.g. by non-homologous end joining).

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 (sometimes by 100-fold) in cells defective in DNA mismatch repair [15]

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 (causing a very high mutation rate), 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. [16]

Diagnosis

Carcinomas can be definitively diagnosed through biopsy, including fine-needle aspiration (FNA), core biopsy, or subtotal removal of single node,. [17] 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, (e.g.hepatocellular carcinoma, renal cell carcinoma).

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 [19] and bladder cancer [20] 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. [21]

The UICC/AJCC TNM systems are most often used.[ clarification needed ] [22] 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:

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. [23] [24]

Epidemiology

While cancer is generally considered a disease of old age, children can also develop cancer. [25] In contrast to adults, carcinomas are exceptionally rare in children.[ citation needed ].

The two biggest risk factors for ovarian carcinoma are age and family history. [26]

Related Research Articles

Adenocarcinoma carcinoma that has material basis in abnormally proliferating cells, derives from epithelial cells, which originate in glandular tissue

Adenocarcinoma is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them.

Surface epithelial-stromal tumor ovarian tumor that is derived_from ovarian surface epithelium

Surface epithelial-stromal tumors are a class of ovarian neoplasms that may be benign or malignant. Neoplasms in this group are thought to be derived from the ovarian surface epithelium or from ectopic endometrial or Fallopian tube (tubal) tissue. Tumors of this type are also called ovarian adenocarcinoma. This group of tumors accounts for 90% to 95% of all cases of ovarian cancer. Serum CA-125 is often elevated but is only 50% accurate so it is not a useful tumor marker to assess the progress of treatment.

Neoplasm abnormal mass of tissue as a result of abnormal growth or division of cells

A neoplasm is a type of abnormal and excessive growth, called neoplasia, of tissue. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and it persists growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass. When it forms a mass, it may be called a tumor.

Grading (tumors) measure of the cell appearance in tumors and other neoplasms

In pathology, grading is a measure of the cell appearance in tumors and other neoplasms. Some pathology grading systems apply only to malignant neoplasms (cancer); others apply also to benign neoplasms. The neoplastic grading is a measure of cell anaplasia in the sampled tumor and is based on the resemblance of the tumor to the tissue of origin. Grading in cancer is distinguished from staging, which is a measure of the extent to which the cancer has spread.

Non-small-cell lung carcinoma type of tumour

Non-small-cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both pre-operatively and post-operatively.

Mixed Müllerian tumor

A malignant mixed Müllerian tumor, also known as malignant mixed mesodermal tumor (MMMT) is a cancer found in the uterus, the ovaries, the fallopian tubes and other parts of the body that contains both carcinomatous and sarcomatous components. It is divided into two types, homologous and a heterologous type. MMMT account for between two and five percent of all tumors derived from the body of the uterus, and are found predominantly in postmenopausal women with an average age of 66 years. Risk factors are similar to those of adenocarcinomas and include obesity, exogenous estrogen therapies, and nulliparity. Less well-understood but potential risk factors include tamoxifen therapy and pelvic irradiation.

Salivary gland tumour human disease

Salivary gland tumours or neoplasms are tumours that form in the tissues of salivary glands. The salivary glands are classified as major or minor. The major salivary glands consist of the parotid, submandibular, and sublingual glands. The minor salivary glands consist of 800-1000 small mucus-secreting glands located throughout the lining of the oral cavity.

Large-cell carcinoma (LCC) is a heterogeneous group of undifferentiated malignant neoplasms that lack the cytologic and architectural features of small cell carcinoma and glandular or squamous differentiation. LCC is categorized as a type of NSCLC which originates from epithelial cells of the lung.

In medicine, desmoplasia is the growth of fibrous or connective tissue. It is also called desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.

Combined small-cell lung carcinoma

Combined small cell lung carcinoma is a form of multiphasic lung cancer that is diagnosed by a pathologist when a malignant tumor arising from transformed cells originating in lung tissue contains a component of small cell lung carcinoma (SCLC) admixed with one components of non-small cell lung carcinoma (NSCLC).

Large cell lung carcinoma with rhabdoid phenotype (LCLC-RP) is a rare histological form of lung cancer, currently classified as a variant of large cell lung carcinoma (LCLC). In order for a LCLC to be subclassified as the rhabdoid phenotype variant, at least 10% of the malignant tumor cells must contain distinctive structures composed of tangled intermediate filaments that displace the cell nucleus outward toward the cell membrane. The whorled eosinophilic inclusions in LCLC-RP cells give it a microscopic resemblance to malignant cells found in rhabdomyosarcoma (RMS), a rare neoplasm arising from transformed skeletal muscle. Despite their microscopic similarities, LCLC-RP is not associated with rhabdomyosarcoma.

Epithelial-myoepithelial carcinoma of the lung is a very rare histologic form of malignant epithelial neoplasm ("carcinoma") arising from lung tissue.

HOHMS is the medical acronym for "Higher-Order HistoMolecular Stratification", a term and concept which was first applied to lung cancer research and treatment theory.

Giant-cell carcinoma of the lung (GCCL) is a rare histological form of large-cell lung carcinoma, a subtype of undifferentiated lung cancer, traditionally classified within the non-small-cell lung carcinomas (NSCLC).

Adenosquamous lung carcinoma (AdSqLC) is a biphasic malignant tumor arising from lung tissue that is composed of at least 10% by volume each of squamous cell carcinoma (SqCC) and adenocarcinoma (AdC) cells.

Salivary gland–like carcinomas of the lung generally refers a class of rare cancers that arise from the uncontrolled cell division (mitosis) of mutated cancer stem cells in lung tissue. They take their name partly from the appearance of their abnormal cells, whose structure and features closely resemble those of cancers that form in the major salivary glands of the head and neck. Carcinoma is a term for malignant neoplasms derived from cells of epithelial lineage, and/or that exhibit cytological or tissue architectural features characteristically found in epithelial cells.

Basaloid squamous cell carcinoma (Bas-SqCC) is an uncommon histological variant of lung cancer composed of cells exhibiting cytological and tissue architectural features of both squamous cell lung carcinoma and basal cell carcinoma.

Squamous-cell carcinoma of the lung lung cancer

Squamous-cell carcinoma (SCC) of the lung is a histologic type of non-small-cell lung carcinoma (NSCLC). It is the second most prevalent type of lung cancer after lung adenocarcinoma and it originates in the bronchi. Its tumor cells are characterized by a squamous appearance, similar to the one observed in epidermal cells. Squamous-cell carcinoma of the lung is strongly associated with tobacco smoking, more than any other form of NSCLC.

Bartholin gland carcinoma vulva carcinoma that has material basis in abnormally proliferating cells derives from epithelial cells and is located in Bartholins gland

Bartholin gland carcinoma is an uncommon type of malignancy in the Bartholin gland that accounts for 1% of all vulvar malignant neoplasms. It is most common in women in their mid-60s. The tumor can become large before a woman is aware of symptoms. One of the first symptoms can be dyspareunia. In other instances a woman may find a mass or ulcer in the vulva area. Many clinicians assume that an enlarged Bartholin gland is malignant in postmenopausal woman until proven otherwise. The growth of the tumor can spread to nearby areas such as the ischiorectal fossa and inguinal lymph nodes. Approximately 50% of bartholin gland carcinomas originate from squamous cell carcinomas. Another uncommon characteristic of Bartholin gland malignancies is that the growth of a lesion originates from the three types of epithelial tissue present in the gland: mucinous, transitional, and squamous.

Squamous cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that result from squamous cells. These cells form the surface of the skin and lining of hollow organs in the body and line the respiratory and digestive tracts.

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Classification
D