Porth's Essentials of Pathophysiology, 4e

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Neoplasia

C h a p t e r 7

The seeding of cancer cells into body cavities occurs when a tumor erodes and sheds cells into these spaces. 2,3 Most often, the peritoneal cavity is involved, but other spaces such as the pleural cavity, pericardial cavity, and joint spaces may be involved. Seeding into the perito- neal cavity is particularly common with ovarian can- cers. Similar to tissue culture, tumors in these sites grow in masses and often produce fluid (e.g., ascites, pleural effusion). 2 The seeding of cancers is often a concern dur- ing the surgical removal of cancers, where it is possible to inadvertently introduce free cancer cells into a body cavity such as the peritoneal cavity. 8 Metastatic Spread The term metastasis is used to describe the development of a secondary tumor in a location distant from the pri- mary tumor. 2,3 Metastatic tumors frequently retain many of the microscopic characteristics of the primary tumor from which they were derived. Because of this, it usually is possible to determine the site of the primary tumor from the cellular characteristics of the metastatic tumor. Some tumors tend to metastasize early in their devel- opmental course, while others do not metastasize until later. Occasionally, a metastatic tumor will be found far advanced before the primary tumor becomes clinically detectable. Malignant tumors disseminate by one of two path- ways: lymph channels (lymphatic spread) or blood ves- sels (hematogenous spread). 2 Lymphatic spread is more typical of carcinomas, whereas hematogenous spread is favored by sarcomas. Lymphatic Spread. In many types of cancer, the first evidence of disseminated disease is the presence of tumor cells in the lymph nodes that drain the tumor area. 9 When metastasis occurs by way of the lymphatic channels, the tumor cells lodge first in the initial lymph node that receives drainage from the tumor site. Once in this lymph node, the cells may die because of the lack of a proper environment, remain dormant for unknown reasons, or grow into a discernible mass (Fig. 7-4). If they survive and grow, the cancer cells may spread from more distant lymph nodes to the thoracic duct, and then gain access to the blood vasculature. Furthermore, can- cer cells may gain access to the blood vasculature from the initial node and more distant lymph nodes by way of tumor-associated blood vessels that may infiltrate the tumor mass. The term sentinel node is used to describe the ini- tial lymph node to which the primary tumor drains. 10 Because the initial metastasis in breast cancer is almost always lymphatic, lymphatic spread and, therefore, extent of disease may be determined through lymphatic mapping and sentinel lymph node biopsy. This is done by injecting a radioactive tracer and blue dye into the tumor to determine the first lymph node in the route of lymph drainage from the cancer. Once the sentinel lymph node is identified, it is examined to determine the presence or absence of cancer cells. The procedure is also used to map the spread of melanoma and other

cancers that have their initial metastatic spread through the lymphatic system. Hematogenous Spread. With hematogenous spread, cancer cells commonly invade capillaries and venules, whereas thicker-walled arterioles and arteries are rela- tively resistant. With venous invasion, blood-borne neo- plastic cells follow the venous flow draining the site of the neoplasm, often stopping in the first capillary bed they encounter. Since venous blood from the gastroin- testinal tract, pancreas, and spleen is routed through the portal vein to the liver, and all vena caval blood flows to the lungs, the liver and lungs are the most frequent metastatic sites for hematogenous spread. 2,3 Although the site of hematologic spread usually is related to vascular drainage of the primary tumor, some tumors metastasize to distant and unrelated sites. For example, prostatic cancer preferably spreads to bone, bronchogenic cancer to the adrenals and brain, and neu- roblastomas to the liver and bones. The selective nature of hematologic spread indicates that metastasis is a finely orchestrated and multistep process, in which only a small, select clone of cancer cells has the right combina- tion of gene products to perform all of the steps needed for establishment of a secondary tumor (Fig. 7-5). To metastasize, a cancer cell must be able to break loose from the primary tumor, invade the surrounding extra- cellular matrix, gain access to a blood vessel, survive its passage in the bloodstream, emerge from the blood- stream at a favorable location, invade the surrounding tissue, and begin to grow and establish a blood supply. Considerable evidence suggests that cancer cells capable of metastasis secrete enzymes that break down the surrounding extracellular matrix, allowing them to FIGURE 7-4. Metastatic carcinoma in periaortic lymph nodes. Aorta has been opened and nodes bisected. (From Strayer DS, Rubin E. Neoplasia. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams & Wilkins; 2012:167.)