Carcinomas

ALSO KNOWN AS: Epithelial cell cancer

RELATED CONDITIONS: Dysplasia, metaplasia

DEFINITION: A carcinoma is any type of cancer arising from epithelial cells. It is distinguished from cancers of connective tissue (sarcomas), cancers of blood-forming cells (leukemias and lymphomas), and germ-cell tumors (teratomas). Carcinomas arising from stratified squamous epithelium are termed squamous cell carcinomas; those arising from glandular epithelium are termed adenocarcinomas.

Risk factors: Risk factors fall into two categories: environmental and hereditary. Environmental risk factors include exposure to carcinogenic chemicals ionizing radiation, or infection with oncogenic viruses. Thousands of carcinogenic chemicals are known, and many are subject to strict regulations regarding exposure. Exposure to ionizing radiation, the most important source of which is the ultraviolet portion of sunlight, is another risk factor. Other important risk factors are inborn genetic variations that predispose individuals to particular cancers and immune system dysfunction.

Etiology and the disease process: Epithelial cells are more prone to malignant transformation than other types of cells because they are routinely exposed to the outside environment. Therefore, carcinoma is far more prevalent than sarcoma, leukemia, or other forms of cancer. The etiology of carcinoma hinges on cellular alterations that confer several key traits on the cell: unregulated growth, stimulation of new blood vessel formation, tissue invasion, and metastatic potential. Infection by oncogenic viruses causes carcinoma by the introduction of foreign genes into the cell; these oncogenic genes (oncogenes) can confer the attributes of malignancy to the infected cells. Gene disruption can cause carcinoma via abnormal activation of oncogenes or, alternatively, by abnormal inactivation of tumor-suppressor genes.

Incidence: Carcinoma is by far the most prevalent form of cancer, accounting for more than 90 percent of new cancer cases and cancer deaths. According to the U.S. Centers for Disease Control and Prevention, in 2021, there were approximately 1.77 million new cases of cancer reported in the U.S. In 2022, 608,366 cancer-related deaths were recorded, and approximately 547,500 of these were types of carcinomas.  

Symptoms: Symptoms of early carcinoma vary widely according to the epithelial cells affected and their growth pattern. Advanced or terminal carcinoma symptoms include cachexia, pain, fatigue, and depression.

Screening and diagnosis: Carcinoma screening consists of carefully inspecting epithelial cells at risk and blood tests for circulating tumor markers. Inspection for skin cancer may be as straightforward as looking for suspicious changes on the skin, whereas screening for cervical cancer involves scraping or brushing cells from the uterine cervix followed by staining and microscopic examination (a Pap smear). Blood tests can also screen for carcinoma based on shedding tumor-specific molecules into the circulation. A blood test for prostate-specific antigen (PSA) is used to screen men at risk for prostate cancer; those with high levels are then candidates for diagnostic biopsy. Pathologists usually diagnose carcinoma based on microscopic examination of biopsied tissue. Features of carcinoma include cellular traits such as abnormally large nuclei, loss of multicellular organization, and disruption of the basement membrane. Carcinoma staging is based on searching for malignant cells in adjacent structures and lymph nodes. Carcinoma staging uses the International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC) system that describes the tumor itself, lymph node involvement, and metastatic lesions; however, other staging systems are also used, such as Dukes' classification of colon cancer.

Treatment and therapy: Treatment options for carcinoma include surgery, chemotherapy, radiotherapy, immunotherapy, monoclonal antibody therapy, and other less common approaches. Treatment plans are made based on the disease grade and stage and the patient's functional status. Surgical treatment (mechanical removal of the tumor) reliably reduces the tumor burden and offers complete resection as the best outcome. Examples include surgical removal of the breast (mastectomy) or prostate (prostatectomy). chemotherapy (systemic administration of anticarcinoma drugs) can damage tumor cells anywhere in the body, usually by interfering with deoxyribonucleic acid (DNA) replication. Many chemotherapy regimens harm healthy tissue as a dose-limiting toxicity. Radiotherapy uses high-energy electromagnetic radiation (X or gamma rays) to damage or kill cancer cells; radiation can be delivered from the outside or by implantation of radioactive pellets (brachytherapy). Immunotherapy is an attempt to attack carcinoma cells with the patient's immune cells. Monoclonal antibody therapy depends on knowledge of signal transduction pathways and uses antibodies to block or disrupt the malignant cells' growth. An example includes the use of monoclonal antibodies against human epidermal growth factor receptor 2 (HER2), such as trastuzumab, to interfere with signals generated by the HER2 receptor in breast cancer.

Prognosis, prevention, and outcomes: Although some types of carcinomas are quite deadly, many forms are indolent and manageable. The prognosis depends mostly on the type of carcinoma, the histologic grade, and the anatomic stage. Prevention efforts can reduce the incidence of carcinomas within populations and take the form of avoiding or reducing exposure to carcinogens. Examples include smoking cessation campaigns to prevent some cases of lung cancer and the promotion of sunscreen use to prevent some cases of melanoma. Individuals may further reduce their risk of cancer by losing weight and being physically active. Outcomes continue to improve because of the integration of treatments and supportive care.

Immunotherapy is a relatively new form of cancer treatment. The first of these types of drugs first began to be tested and approved in the 2020s. The distinguishing features of immunotherapies is that they enable the body's immune system to both detect and combat cancer. They can be targeted against specific cancers in contrast to non-targeted treatments such as chemotherapy, which will destroy both cancerous and healthy tissues alike. Immunotherapies work by removing blockers that cancer cells use to hide or disguise their presence. Although immunotherapy treatments have undergone significant advancements in the past several decades, more research and development are required in areas such as the reduction of side effects.

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