Carcinoma

Carcinoma is a malignant neoplasm arising from epithelial cells — the cells that line surfaces and form glands. Carcinomas are the most common category of human cancer and include the major epithelial malignancies of the skin, lung, breast, colon, prostate, and many other organs. They are classified principally by their pattern of differentiation, with adenocarcinoma (glandular) and squamous cell carcinoma (squamous epithelial) among the most frequent types.

Definition

A carcinoma is a malignant neoplasm of epithelial cell origin, classified by its differentiation pattern (for example glandular in adenocarcinoma or squamous in squamous cell carcinoma) and capable of local invasion and metastasis.

Scope

The entry covers the epithelial origin of carcinoma, its main histologic subtypes (notably adenocarcinoma and squamous cell carcinoma), the concept of in situ versus invasive disease, grading by differentiation, and staging by anatomic extent. It treats carcinoma as a category of malignant neoplasm; the broader principles of malignancy and of metastatic spread are developed in sibling topics.

Core questions

• What tissue of origin defines a carcinoma?
• How do adenocarcinoma and squamous cell carcinoma differ?
• What distinguishes carcinoma in situ from invasive carcinoma?
• How are carcinomas graded and staged?
• How do precursor lesions and risk factors relate to carcinoma development?

Key concepts

• Epithelial cell origin
• Adenocarcinoma (glandular)
• Squamous cell carcinoma
• Carcinoma in situ versus invasive carcinoma
• Basement-membrane invasion
• Grading by differentiation
• Precursor lesions and carcinogenesis

Key theories

Multistep epithelial carcinogenesis

Vogelstein and colleagues showed, in the colorectal model, that carcinoma develops through an ordered accumulation of genetic alterations as epithelium progresses from normal mucosa through adenoma to invasive carcinoma — a paradigm for stepwise epithelial tumor progression.

Mechanisms

Carcinomas arise when epithelial cells acquire the malignant capabilities of invasion and metastasis through accumulated genetic and epigenetic change. A key conceptual stage is carcinoma in situ, in which malignant epithelial cells are confined above the basement membrane; invasion is defined by breach of that membrane and infiltration of underlying stroma. Subtyping rests on the differentiation the tumor recapitulates — gland formation in adenocarcinoma, keratinization and intercellular bridges in squamous cell carcinoma — and grade reflects how closely the tumor resembles its normal epithelium. The colorectal adenoma-carcinoma sequence exemplifies multistep carcinogenesis, in which ordered genetic alterations drive progression from normal mucosa to invasive carcinoma. Specific carcinogens and oncogenic infections also contribute; for instance, human papillomavirus is associated with a distinct subset of head and neck squamous cell carcinomas.

Clinical relevance

Carcinomas constitute the majority of cancers encountered in adults, and their histologic subtype, grade, and stage frame how the disease is described and studied. Distinctions such as in situ versus invasive disease and the molecular or viral context of a tumor (for example HPV-associated squamous cell carcinoma) are used to characterize tumor biology. This entry is a reference orientation and does not provide diagnostic criteria or treatment guidance for any individual.

Epidemiology

Carcinomas account for the large majority of malignant neoplasms in adults, and several of the most common and most lethal cancers worldwide — including lung, breast, colorectal, and prostate cancers — are carcinomas. Incidence and outcome vary widely by subtype, organ, and biological context; HPV-positive oropharyngeal squamous cell carcinoma, for example, has been associated with more favorable survival than its HPV-negative counterpart.

Evidence & guidelines

Carcinomas are classified by the WHO Classification of Tumours series and staged by the AJCC/UICC TNM system, with organ-specific protocols describing the features pathologists report. General principles are consolidated in references such as Robbins & Cotran Pathologic Basis of Disease. These sources describe classification and staging conventions rather than prescriptive clinical protocols.

History

The recognition that malignant tumors could be classified by tissue of origin established carcinoma as the designation for epithelial malignancies, distinct from sarcomas of mesenchymal origin. Twentieth-century work clarified the in situ-to-invasive continuum, and Vogelstein's multistep model of colorectal tumorigenesis provided a molecular paradigm for epithelial carcinogenesis. The later identification of human papillomavirus as a driver of a biologically distinct subset of squamous cell carcinomas further refined how carcinomas are subclassified.

Key figures

• Bert Vogelstein
• Maura Gillison

Seminal works

• vogelstein-1988
• amin-2017

Frequently asked questions

What is the difference between a carcinoma and a sarcoma?

Carcinomas arise from epithelial cells (those lining surfaces or forming glands), whereas sarcomas arise from mesenchymal tissues such as bone, muscle, fat, or connective tissue. Carcinomas are far more common in adults.

What does 'carcinoma in situ' mean?

Carcinoma in situ refers to malignant epithelial cells that remain confined above the basement membrane and have not invaded the underlying tissue. Crossing the basement membrane marks the transition to invasive carcinoma.