Metastasis

Metastasis
Other names	Metastatic disease
Illustration showing hematogenous metastasis
Pronunciation	Metastasis /mᵻˈtastəsɪs/ metastases /mə ˈtæs tə siːz/
Specialty	Oncology

Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body;^[1] the term is typically used when referring to metastasis by a cancerous tumor.^[2] The newly pathological sites, then, are metastases (mets).^[3][4] It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues.^[5]

Cancer occurs after cells are genetically altered to proliferate rapidly and indefinitely. This uncontrolled proliferation by mitosis produces a primary heterogeneic tumour. The cells which constitute the tumor eventually undergo metaplasia, followed by dysplasia then anaplasia, resulting in a malignant phenotype. This malignancy allows for invasion into the circulation, followed by invasion to a second site for tumorigenesis.

Some cancer cells, known as circulating tumor cells (CTCs), are able to penetrate the walls of lymphatic or blood vessels, and circulate through the bloodstream to other sites and tissues in the body.^[6] This process, known respectively as lymphatic or hematogenous spread, allows not only single cells but also groups of cells, or CTC clusters, to travel. Evidence suggests that CTC clusters may retain their multicellular configuration throughout metastasis, enhancing their ability to establish secondary tumors.^[7] This perspective aligns with the cancer exodus hypothesis, which posits that maintaining this cluster structure contributes to a higher metastatic potential. Metastasis is one of the hallmarks of cancer, distinguishing it from benign tumors.^[8] Most cancers can metastasize, although in varying degrees. Basal cell carcinoma for example rarely metastasizes.^[8]

When tumor cells metastasize, the new tumor is called a secondary or metastatic tumor, and its cells are similar to those in the original or primary tumor.^[9] This means that if breast cancer metastasizes to the lungs, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called metastatic breast cancer, not lung cancer. Metastasis is a key element in cancer staging systems such as the TNM staging system, where it represents the "M". In overall stage grouping, metastasis places a cancer in Stage IV. The possibilities of curative treatment are greatly reduced, or often entirely removed when a cancer has metastasized.